Statins, an anti-hyperlipidemic drug, is associated with skeletal muscle myopathy, which may be severe enough to discontinue statin therapy. This study assessed the effect of mesenchymal stem cells (MSCs) versus intermittent fasting on simvastatin induced myopathy in rats and studied the possible autophagy role. This study included forty adult female and four male Sprague Dawely rats. Male rats were used for MSCs isolation. The female rats were divided as follow: Group I served as the control group. Group II (the myopathy group) rats were given a daily oral dose of simvastatin for 30 days. Group III (discontinuation group) rats were given a daily oral dose of simvastatin for 30 days and and were left without treatment for 15 days. Group IV (the intravenous stem cell group) rats were given a daily oral dose of simvastatin for 30 days and then a single stem cell injection was administered intravenously. Group V (the intermittent fasting group) rats were given a daily oral dose of simvastatin for 30 days and then an intermittent fasting protocol was started. Gastrocnemius muscle contractility, histopathological examination plus serum creatine kinase (CK) level, autophagy markers (LC3 and P62) expression and MSCs homing by PCR were carried out. Simvastatin significantly altered contractile properties, induced atrophy of skeletal muscle, increased CK, LC3 and P62 levels. Meanwhile, MSCs injection and intermittent fasting significantly restored all these alterations which were confirmed by histopathological improvement. They reduced skeletal muscle atrophy and CK level, and improve the skeletal muscle contractility and autophagy flux. In conclusion: Statin myopathy is revealed to be due to autophagy flux inhibition. MSCs injection and intermittent fasting induced pronounced skeletal muscle regeneration with improvement of functions. The improvement recorded in intermittent fasting group was significantly better than that observed with MSC injected group.