Background Myopathies are diseases of skeletal muscle in which there is a primary functional or structural impairment. No standard therapeutic guidelines exist. The use of stem cells may provide dramatic advances in their treatment. Aim of the work To evaluate the potential therapeutic effect of bone marrow mesenchymal stem cells (BM-MSCs) introduced by two different routes; intravenous and intramuscular on experimentally induced myopathy in rats Material and Methods Sixty adult male rats were divided into five groups. Group I: control. Group II (myopathy group): Rats were given daily oral dose of simvastatin for six weeks. Group III (intramuscular stem cells group): Rats were given daily oral dose of simvastatin for six weeks then single stem cells injection was administered intramuscularly. Group IV (intravenous stem cells group): Rats were given daily oral dose of simvastatin for six weeks then single stem cells injection was administered intravenously. Group V (recovery group): Rats were given daily oral dose of simvastatin for six weeks and were left without treatment for two weeks. Gastrocnemius muscle samples were processed and examined using histological and immunohistochemical techniques. Results Myopathy group showed disruption of muscle fibers with loss of striation. Separated muscle fibers with areas of myofibrils loss. Disrupted mitochondria, collagen fibers accumulation and marked caspase-3 immune reactivity were noticed. Intramuscular stem cells group showed histological architecture and ultrastructure near to control group except for slight separation of the myofibrils bundles. Intravenous stem cells group showed small areas of muscle fibers destruction and loss of myofibrils. Recovery group showed picture similar to group II. Conclusion MSCs administered either intramuscular or intravenous have therapeutic potentials for statin induced myopathy. However, intramuscular route is more effective.