In this study, the role of CoQ10 and berberine in the treatment of ischemia-reperfusion injury is researched by analyzing the biochemical effects of CoQ10 and berberine administered after experimental ischemia-reperfusion injury in rats. 32 Sprague-Dawley 200-250 g male rats were randomly divided into four equal groups as weighting, including: control, ischemia-reperfusion (I/R) and experimental groups treated with CoQ10 (10 mg/kg dose, 3 times with 8 h intervals) and berberine (200 mg/kg dose, 3 times with 8 h intervals) that were administered by intragastric way to the I/R+ CoQ10 and I/R+ berberine group before two hours ischemia two hours reperfusion with tourniquet. In the sham group, only gastrocnemius muscle were removed and given no CoQ10 and Berberine. By the completion of reperfusion; all rats were anesthetized with ketamine and xylazine, sacrificed after taking samples to measure levels of blood lactate dehydrogenase (LDH), creatine kinase (CK); MDA, MPO, GSH, SOD, GPx and CAT in blood and muscle tissues. Compared to control group, ischemic-reperfusion injury significantly increased plasma LDH, CK; MDA and MPO levels, decreased GSH, SOD, GPx and CAT activities of blood and muscle tissues. Treatments groups showed significantly decreased MDA and MPO levels, increased GSH levels, SOD, GPx and CAT activities compared to the IR group. Our results suggest that CoQ10 and Berberine may protect or treat against oxidative damage on ischemia-reperfusion injury and that can be benefical treating association with lower extremity ischemia-reperfusion injury.