BACKGROUND: Statins are prescribed to manage hypercholesterolemia. While effective, these medications are associated with adverse effects, particularly myopathy. Cholesterol is essential for muscle function, and its depletion - especially by lipophilic statins - may contribute to muscle damage. Pitavastatin mainly targets hepatic cholesterol synthesis with minimal direct effect on muscle tissue. This study investigates the impact of pitavastatin-induced cholesterol depletion on skeletal muscle. METHODS: Male Sprague-Dawley rats were divided into three groups: control ( RESULTS: Pitavastatin significantly reduced total cholesterol and low-density lipoprotein cholesterol in both ND and HCD groups ( CONCLUSION: Pitavastatin-induced cholesterol depletion increased hepatic and muscle damage markers. Dietary cholesterol may mitigate these effects, highlighting the importance of cholesterol homeostasis in statin therapy.