BACKGROUND AND PURPOSE Drug-induced myopathy is one of the frequent forms of muscle disease, and drugs used for hyperlipidemia, especially the statins are a common culprit, and particularly when combined with a fibrate. Clinicians usually measure plasma levels of three enzymes, creatine kinase (CK), aldolase and lactate dehydrogenase (LDH) for diagnosis of myopathy and determination of its severity. Physical exercise can aggravate statin-associated muscular disease. The question is whether antioxidants like vitamin C (Vit.C) can prevent such myopathy. EXPERIMENTAL APPROACH In this experiment a combination of oral atorvastatin (ATV, 80 mg/kg/day, orally) and gemfibrozil (GMF, 1000 mg/kg/day, orally) was used for ten days plus exercise in days 8, 9 and 10 to induce myopathy in rats. To add physical exercise, the forced swimming test was applied in the last three days. Ascorbic acid (50 mg/kg/day, orally) was added to ATV/GMF plus exercise regimen throughout the 10 days in the treatment group. The mean blood levels of CK, aldolase and LDH were measured in addition to swimming tolerance times. KEY RESULTS There was a significantly lower swimming tolerance time (P < 0.05) and higher CK levels (P < 0.01) in rats receiving ATV/GMF/Vit.C plus exercise compared with rats not taking Vit.C. LDH and aldolase didn’t decrease significantly. CONCLUSIONS & IMPLICATIONS A protective role of vit.C against drug-induced myopathy is suggested by the findings of this study.