Relapse to opioid, even long time after withdrawal, is one of the most important problems of opiate withdrawal programs. Magnesium has been shown that; inhibit glutamate release and induces N-Methyl-D-aspartate (NMDA) antagonistic effects; moreover, glutamate NMDA antagonists contribute to the reinforcement of morphine. In the current study, the effects of magnesium sulfate on the acquisition and reinstatement of morphine-induced conditioned place preference (CPP) in an animal model were investigated. The acquisition and extinction and reinstatement phases induced using morphine 40 and 10mg/kg. J Fundam Appl Sci. 2016, 8(2S), 112-123 113 Magnesium sulfate 300 and 600 mg/kg (not 150mg/kg) reduced morphine dependence.Additionally, tendency of animals to the white compartment of CPP chamber significantly decreased. Magnesium sulfate inhibits morphine tendency and reinstatement probably via NMDA antagonistic effects.