Statins are the most commonly used drugs and the first line treatment for atherosclerotic disorders related to hypercholesterolemia. Myopathy represents the well documented and the most disturbing adverse effects of statins. The underlying mechanism of myopathy is still unknown. The aim of the current study was to evaluate the possible protective role of melatonin in treatment of statin-induced myopathy in rats. Myopathy was determined using biochemical, functional and histopathological examinations. Atorvastatin induced myopathy through prominent muscle wasting and significant increase in serum CK, lactate dehydrogenase and myoglobin levels. Motor activity, evaluated by rotarod test, showed that atorvastatin greatly reduced rats’ motor activity compared to melatonin treated one. We also found that atorvastatin induced ROS generation and increased oxidative stress through evaluation of GSH, MDA, SOD and Nitrite levels. Melatonin significantly attenuated atorvastatin-induced oxidative stress. Ultrastructure examination showed that co-treatment with melatonin reduced degenerative changes and necrosis in gastrocnemius muscle. In conclusion, these results suggest that melatonin has a prominent muscle-protective role in statin-induced myopathy possibly through its antioxidant activity.