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The Macedonian and Seleucid wars were a series of conflicts fought by Rome during and after the second Punic war, in the eastern Mediterranean, the Adriatic, and the Aegean. Along with the Punic wars, they resulted in Roman control or influence over the entire Mediterranean basin.

During the Second Punic War, Philip V of Macedon allied himself with Hannibal. Fearing possible reinforcement of Hannibal by Macedon, Rome dispatched forces across the Adriatic. Roman legions (aided by allies from the Aetolian League and Pergamon after 211 BC) did little more than skirmish with Macedonian forces and seize minor territory along the Adriatic coastline in order to "combat piracy". Rome's interest was not in conquest, but in keeping Macedon, the Greek city-states, and political leagues carefully divided and non-threatening. The war ended indecisively in 205 BC with the Treaty of Phoenice. While a minor conflict, it opened the way for Roman military intervention in Greece.

In 201 BC, ambassadors from Pergamon and Rhodes brought evidence before the Roman Senate that Philip V of Macedon and Antiochus III of the Seleucid Empire had signed a non-aggression pact. Although some scholars view this "secret treaty" as a fabrication by Pergamon and Rhodes, it resulted in Rome launching the second Macedonian war, with aid from its Greek allies. It was an indecisive conflict until the Roman victory at the Battle of Cynoscephalae in 197 BC. After Rome imposed the Treaty of Tempea, Philip V was forbidden to interfere with affairs outside his borders, a condition he adhered to for the rest of his life. In 194 BC Rome declared Greece "free", and withdrew completely from the Balkans. It seemed that Rome had no further interest in the region.

Following the second Macedonian war, the Aetolian League was unhappy with the amount of territory ceded to them by Rome as "reward" for their aid. In response, they "invited" Antiochus III of Seleucid Syria to assist them in freeing Greece from "Roman oppression". As his military advisor, Hannibal had urged Antiochus not to enter Greece with so few troops, however Antiochus sent a small force into Greece in 192 BC, to which Rome responded by sending its legions back into Greece, driving out the Seleucids.

Possibly in part because he had given Hannibal shelter, Rome sent a force of 30,000 troops under Scipio Africanus into Asia Minor to intercept Antiochus. Upon receipt of the knowledge that the Romans were afoot, Antiochus was now faced with a daunting choice. Either he must surrender in a very humiliating manner and flee back into Asia or face the Romans in a geographical position that would serve as disadvantagous for a numerically superior force. Opting for the latter, Antiochus chose Thermopylae. He was quickly outflanked by the Roman advance just as the Spartans had been by the Persians 300 years earlier. This resulted in the Roman victories at Thermopylae (191 BC) and the Battle of Magnesia (190 BC). These victories on the part of Rome in Asia Minor resulted in the forced signing by Antiochus of the Treaty of Apamea (188 BC), ceding Seleucid territory to Rome and Pergamon, and imposing a war indemnity of 15,000 talents of silver.

Upon Philip's death in Macedon (179 BC), his son, Perseus of Macedon, attempted to restore Macedon's international influence, and moved aggressively against his neighbors. When Perseus was implicated in an assassination plot against an ally of Rome, the Senate declared the third Macedonian War. Initially, Rome did not fare well against the Macedonian forces, but in 168 BC, Roman legions smashed the Macedonian phalanx at the Battle of Pydna. Perseus was later captured and the kingdom of Macedon divided into four puppet republics that Rome controlled.

For several years, Greece was peaceful until a popular uprising in Macedon rose up under Andriscus, who claimed to be a son of Perseus. Rome once again dispatched its legions into Greece, and thoroughly put down the Macedonian rebellion. This time, Rome did not withdraw from the region, forming the Roman province of Macedonia, establishing a permanent Roman foothold on the Greek peninsula.

In response, the remaining free Greek powers of the Achaean League, rose up against Roman presence in Greece. This is sometimes referred to as the Achaen War, 146 BC, noted for its short duration and its timing right after the fall of Macedonia. Resentment at Roman high handedness caused the cities of the Achaen League to declare war on Rome. Until this time, Rome had only campaigned in Greece in order to fight Macedonian forts, allies or clients. Rome's military supremacy was well established and generally admitted, having defeated Macedonia and its vaunted Phalanx already on 3 occasions, and defeating superior numbers against the Seluecids in Asia. The Achaen leaders must have known that this declaration of war against Rome was hopeless, as Rome had triumphed against far stronger and larger opponents, the Roman legion having proved its supremacy over the Eastern phalanx. Polybius blames the demagogues of the cities of the league for inspiring the population into a suicidal war. Nationalist stirrings, the idea of triumphing against superior odds motivated the league into this rash decision. Hadn't these same cities' phalanxes defeated far superior numbers in the Persian Wars 300 years previously? Rome's patience was at an end as the League was swiftly defeated, and as an object lesson, Rome utterly destroyed the ancient city of Corinth in 146 BC, the same year that Carthage was destroyed. The Macedonian wars had come to an end, along with Greek independence. Greece became provinces of Achaea, Epirus. The early years of conquest was marked by enslavement, and looting. Rome, while still a Republic, now possessed an Empire throughout the Western and Central Mediterranean that now outnumbered the Roman homelands in Italy.

See main article: Roman Republic