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Objective: In this study, the effects of estradiol valerate and raloxifenea selective estrogen receptor modulator; (SERM) on morphine induced sensitization were examined in mice memory, according to the step-down passive avoidance task. Method:The mice received morphine or estradiol and raloxifene for three days alone or in combination with morphine. After a drug free period of 5 days, the subjects received saline or morphine as pre- training treatments followed by a pre-test saline administration. The memory retrieval was evaluated using step-down passive avoidance test both on the training and test day. Results:The results illustrated that the three- day administration of morphine induced sensitization through the enhancement of memory retrieval (morphine induced sensitization in mice memory). Both the three- day administration of estradiol valerate alone and with morphine (5 mg/kg) restored memory. On the other hand, the three- day administration of raloxifene had no effect on memory retrieval alone, but declined morphine induced sensitization in mice memory. Conclusion:The results of the study indicated that there is an interaction between estrogen receptor modulators and morphine induced sensitization in mice memory.