The Euphrates was the ideal boundary of the territory of Israel. It was God’s promise to Abraham

Ancient Israel’s captors, Assyria and Babylon, had come from the great river Euphrates. In John’s day it also marked the eastern boundary of Rome’s influence, beyond which barbarian powers such as Parthia threatened the empire’s peace. This river represents that which keeps civil chaos and wanton violence at bay. The release of its four destructive angels here, like the drying of its waters in 16:12–16, unleashes unprecedented bloodshed and suffering.

We have to add another fact to all this. We have frequently seen how the pictures of John are coloured by actual historical circumstances. The most dreaded warriors in the world were the Parthian cavalry; and the Parthians lived beyond the Euphrates. It may well be that John was visualizing a terrible descent of the Parthian cavalry on all humanity.

The overall picture painted is that despite the upheavals, tragedies, and overwhelming loss of life generated by the angels of the fifth and sixth trumpets, men continue to reject the one true God in favor of the gods of their own manufacturing, and worse still, even of the demonic spirits that enslave them. In turn, this causes them to demonstrate in their ethical and moral practices continued depravity and lack of regard for the things of God. Their lives became steeped in violence and esoteric practices of various kinds, including those induced by the introduction of foreign substances. There is a callous disregard for the will and purpose of God.