OBJECTIVE To evaluate the effects of melatonin on endometriotic lesions induced by implanting human endometriotic cells in SCID mice. MATERIALS AND METHODS Prospective, randomized, controlled, experimental study. Experimental Research Center of Yeditepe University (YUDETAM). Thirty female, non-pregnant, nulligravid severe combined immunodeficient (SCID) mice. Endometriotic cells collected from patients with endometriosis were implanted subcutaneously in 30 SCID mice. These mice were randomized into two study groups: in the first group, mice were administered melatonin (20 mg/kg/day) following induction of endometriosis for four weeks; in the second group, nothing was administered. All the mice were given a high dose of exogenous estradiol (50 µg/kg/d, twice weekly). Four weeks after inoculation, necropsies were performed and endometriotic lesions were collected. All the lesions were evaluated histopathologically and the levels of SOD and MDA were assessed in the lesions. RESULTS Successful implantation was observed in the 28 mice that survived. Mean MDA level was 5.0 ± 1.7 and 8.8 ± 2.6 in the melatonin and control groups, respectively (p = 0.01); mean SOD level was 1.1 ± 0.1 and 1.0 ± 0.1 in the melatonin and control groups, respectively (p = 0.49). Mean histopathological score was lower in the melatonin group (p = 0.04). CONCLUSIONS Melatonin was effective in the treatment of experimental endometriosis induced in SCID mice.