The first era in Persian foreign relations in the Middle East accounted for the ancient civilizations and empires which ended upon the rise of Islam. During antiquity, ancient Persia was under the reign of the centralizing powers of Elam, Media, the Achaemenid, the non-Persian Seleucid, the Arsacid or Parthia as well as the Sassanid for more than 3,300 years. Persia under Media, the Achaemenid, the Arsacid and the Sassanid Empires was the principal pillar of the international and regional structure. As such, Iranian relations in the ancient Middle East was positive and cooperative. Nevertheless, it was quasi-negative during the Elamite against Assyria and under the Seleucid Empire. The symmetrical and cooperative approaches between the Persian agent and the international structure is the main feature of ancient Iran’s relations in the Middle East.