King Mithridates I of Parthia took advantage of Antiochus' western problems and attacked from the east, seizing the city of Herat in 167 BC and disrupting the direct trade route to India, effectively splitting the Greek world in two.

Antiochus recognized the potential danger in the east but was unwilling to give up control of Judea.
He sent a commander named Lysias to deal with the Maccabees, while the King himself led the main Seleucid army against the Parthians.
Antiochus had initial success in his eastern campaign, including the reoccupation of Armenia, but he died suddenly of disease in 164 BC.

According to the scroll of Antiochus, when Antiochus heard that his army had been defeated in Judea, he boarded a ship and fled to the coastal cities.
Wherever he came the people rebelled and called him "The Fugitive," so he drowned himself in the sea.

According to the Second Book of Maccabees, he was horrifically injured in the following manner, which eventually led to his death:
5 But the all-seeing Lord, the God of Israel, struck him with an incurable and invisible blow.
As soon as he stopped speaking he was seized with a pain in his bowels, for which there was no relief, and with sharp internal tortures— 6 and that very justly, for he had tortured the bowels of others with many and strange inflictions.
7 Yet he did not in any way stop his insolence, but was even more filled with arrogance, breathing fire in his rage against the Jews, and giving orders to drive even faster.
And so it came about that he fell out of his chariot as it was rushing along, and the fall was so hard as to torture every limb of his body.
8 Thus he who only a little while before had thought in his superhuman arrogance that he could command the waves of the sea, and had imagined that he could weigh the high mountains in a balance, was brought down to earth and carried in a litter, making the power of God manifest to all.
And so the ungodly man’s body swarmed with worms, and while he was still living in anguish and pain, his flesh rotted away, and because of the stench the whole army felt revulsion at his decay.

— 2 Maccabees 9:5-9, NRSV
King Mithridates I of Parthia took advantage of Antiochus' western problems and attacked from the east, seizing the city of Herat in 167 BC and disrupting the direct trade route to India, effectively splitting the Greek world in two.
Antiochus recognized the potential danger in the east but was unwilling to give up control of Judea. He sent a commander named Lysias to deal with the Maccabees, while the King himself led the main Seleucid army against the Parthians. Antiochus had initial success in his eastern campaign, including the reoccupation of Armenia, but he died suddenly of disease in 164 BC.
According to the scroll of Antiochus, when Antiochus heard that his army had been defeated in Judea, he boarded a ship and fled to the coastal cities. Wherever he came the people rebelled and called him "The Fugitive," so he drowned himself in the sea.
According to the Second Book of Maccabees, he was horrifically injured in the following manner, which eventually led to his death:
5 But the all-seeing Lord, the God of Israel, struck him with an incurable and invisible blow. As soon as he stopped speaking he was seized with a pain in his bowels, for which there was no relief, and with sharp internal tortures— 6 and that very justly, for he had tortured the bowels of others with many and strange inflictions. 7 Yet he did not in any way stop his insolence, but was even more filled with arrogance, breathing fire in his rage against the Jews, and giving orders to drive even faster. And so it came about that he fell out of his chariot as it was rushing along, and the fall was so hard as to torture every limb of his body. 8 Thus he who only a little while before had thought in his superhuman arrogance that he could command the waves of the sea, and had imagined that he could weigh the high mountains in a balance, was brought down to earth and carried in a litter, making the power of God manifest to all. And so the ungodly man’s body swarmed with worms, and while he was still living in anguish and pain, his flesh rotted away, and because of the stench the whole army felt revulsion at his decay.
— 2 Maccabees 9:5-9, NRSV
Antiochus IV Epiphanes