BACKGROUND Peripheral nerve damage that requires surgical repair does not result in complete recovery because of collagen scar formation, ischemia, free oxygen radical damage, and other factors. To date, the best treatment method has not yet been determined. In this study, we designed an experimental peripheral nerve injury model, and researched the possible effects of melatonin hormone, based on evidence of its strong antioxidant and cell-protective effects via mimicking the effects of calcium channel blockers. METHODS We randomized 24 healthy female albino rats into three groups: the pinealectomy group, melatonin group, and control group. In the pinealectomy group, craniotomy, pinealectomy, sciatic nerve transection, and coaptation were performed, and 0.9% NaCl was injected intraperitoneally. In the melatonin group, craniotomy (without pinealectomy), sciatic nerve dissection, and coaptation were performed, and melatonin was injected intraperitoneally, instead of NaCl. In the control group, craniotomy (without pinealectomy), sciatic nerve dissection and coaptation, and intraperitoneal NaCl injection were performed. In each group, nerve recovery was evaluated histologically, functionally, and electrophysiologically. Functional and electrophysiologic evaluations were conducted before surgery and at 4 and 12 wk. RESULTS At 4 wk, no significant difference was observed between the groups. However, at 12 wk, significant electrophysiologic and functional improvement was observed only in the melatonin group. CONCLUSIONS Melatonin seems to have a beneficial effect on nerve recovery. However, this effect is not effective at physiologic doses. Future comparative studies with melatonin versus other nerve-regenerating agents are necessary to determine the clinical utility of melatonin hormone.