Abstract: AIM　To observe the effects and mechanism of melatonin (MT) on the immune function of morphine dependent mice. METHODS　A physical dependent mice model was established by repeated subcutaneous injection of morphine. The intensity of morphine withdrawal syndrome was evaluated according to the weight of immune organs, the proliferation reaction of stimulated splenic lymphocytes by Con A, the phago-index of blood primed macrophages and the content of NO induced in the peritoneal macrophage (pMφ). RESULTS　MT reversed the inhibitory effect of morphine on the proliferation ability of splenic lymphocytes and enhanced the phagocytosis of macrophages of morphine dependent mice obviously and prevented the over-release of NO from pMφ. The enhancing effects of MT on the phagocytosis can be prevented by naloxon. CONCLUSION　MT can significantly enhance the immune function of morphine dependent mice and inhibit NO excessive release from pMφ.