Effect of melatonin on toxicity of cadmium (Cd) was studied in male SD rats co-administered daily Cd (1 mg/kg b.w., s.c.) with melatonin (10 mg/kg b.w., i.p.) for 15 days. Cd alone injection decreased GSH concentrations in the liver and RBC by 35% and 43% compared with those in saline-treatment group, but not in the kidney and whole brain. The activity of GSSG-reductase was significantly decreased in the liver of Cd alone injected rats, while melatonin given in combination with Cd failed to prevent the Cd-induced decreased activity of hepatic GSSG-reductase. However, the hepatic GSH concentration decreased by Cd alone was restored by melatonin treatment, and the melatonin also ameliorated Cd-induced histopathological changes in the liver. Therefore, data indicate that melatonin restores the reduction of hepatic GSH level induced with Cd regardless of GSSG-reductase activity, and suggests that melatonin may ameliorate Cd-induced hepatotoxicity.