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Achaemenid Empire

Ernst Herzfeld suggested that Bactria belonged to the Medes before its annexation to the Achaemenid Empire by Cyrus the Great in sixth century BC, after which it and Margiana formed the twelfth satrapy of Persia. After Darius III had been defeated by Alexander the Great, the satrap of Bactria, Bessus, attempted to organize a national resistance but was captured by other warlords and delivered to Alexander. He was then tortured and killed.

Under Persian rule, many Greeks were deported to Bactria, so that their communities and language became common in the area. During the reign of Darius I, the inhabitants of the Greek city of Barca, in Cyrenaica, were deported to Bactria for refusing to surrender assassins. In addition, Xerxes also settled the "Branchidae" in Bactria; they were the descendants of Greek priests who had once lived near Didyma (western Asia Minor) and betrayed the temple to him. Herodotus also records a Persian commander threatening to enslave daughters of the revolting Ionians and send them to Bactria. Persia subsequently conscripted Greek men from these settlements in Bactria into their military, as did Alexander later.