The process of formation and development of Iranian cities, like any other cities, in the Islamic period can be attributed to different geographical, historical, political as well as economic, commercial, cultural and religious factors.Kashafrood plain in Khorāsan, where the holy city Mashhad located, enjoys many desired environmental factors such as freshwater, springs and rivers, good climate, fertile soil, rich herbaceous cover and green pasturages which have rendered attraction and provided settlements for human groups from the old times. Further more location of Mashhad near the borders of central Asian tribes had given sensitivity to this town as a strategic military location after the Timurid period.In this paper I triy to survey the effect of historical and political factors of the Safavid period on development of the holy city of Mashhad.