Objective: To investigate the effect of NG-nitro-L-arginine (NO2Arg) on psychical dependence induced by opiates on the basis of improved conditioned place preference model in mice. Methods:The time in biased side was recorded before and after 4 mg/kg NO2Arg administration in morphine and dihydroetorphine psychically dependent mice. Results: 4 mg/kg NO2Arg could significantly increase the time in biased side in morphine and dihydroetorphine psychically dependent mice. The time in biased side was increased from (6.09±2.02), (7.98±0.72) min to (9.31±1.10), (9.48±1.21) min (P<0.01). Conclusion: NO2Arg could reverse the psychical dependence induced by opiates, suggesting that NO plays an important role in the development of opiate psychical dependence.