Diodotus, governor for the Bactrian territory, asserted independence in around 245 BCE, although the exact date is far from certain, to form the Greco-Bactrian Kingdom. This kingdom was characterized by a rich Hellenistic culture and was to continue its domination of Bactria until around 125 BCE when it was overrun by the invasion of northern nomads. One of the Greco-Bactrian kings, Demetrius I of Bactria, invaded India around 180 BCE to form the Indo-Greek Kingdoms.

The rulers of Persis, called Fratarakas, also seem to have established some level of independence from the Seleucids during the 3rd century BCE, especially from the time of Vahbarz. They would later overtly take the title of Kings of Persis, before becoming vassals to the newly formed Parthian Empire.