Introduction: Atorvastatin was chosen for this model because its elimination half-life is nearly 14 hours, a property that stimulates the drug’s efficacy for lowering LDL compared with other statins. Furthermore, it is given in an active form that prolongs its effect on HMG-CoA reductase. Therefore, muscle impairment was intensified by Atorvastatin. Co-Q10 acts as a free radical scavenger in skeletal muscle mitochondria. Vitamin D is a strong antioxidant which maintains the stable activities of the mitochondria. Aim of the study: This work aimed to study changes that occur in rat skeletal muscle during atorvastatin administration and the prophylactic role of coenzyme Q10 and vitamin D. Material and methods: Fifty adult male albino rats were separated into five equal groups. Control group, Statin group, rats were received Atorvastatin at a dose 50 mg/kg/day , liquefied in distilled water and given by gastric tube for 4 weeks. Statin & Coenzyme Q10 treated group at which rats received Coenzyme Q10 at dosage of 3 mg/kg b.wt. during the period of statin treatment. Statin &Vit D treated group at which , rats were treated with statin like that of group II and given Vit D orally at dosage of 0.5μg/kg/day and Withdrawal group at which the rats retained for one month without treatment after 4 weeks of statin treatment. Skeletal muscle tissue was examined for histopathological and immunohistochemical changes. Results:The group treated with Atorvastatin revealed degenerated and disorganized muscle fibers. Also numerous collagen fibers were present within the CT septa in the masson & Van Gieson stained skeletal muscle sections. Strong KI-67 immunoreactivity and weak Desmin and Myogenin immune-expression. Coenzyme Q10 and vit D decrease the effect of statins on skeletal muscle tissue , but Coenzyme Q10 shown a significant diminution in collagen fibers deposition, KI-67 immunoreactivity and significant increase in Desmin & Myogenin immuno expression compared with that in Statin treated group.