Objective: Ischemia-reperfusion (IR)injury is associated with various clinical conditions, such as myocardial infarction, shock, and surgery under vascular occlusion. We aimed to investigate the protective and therapeutic effects of apocynin (AP)on liver injury induced by IR in an in vivo rat model. Methods: Thirty-two rats were randomly divided into 4 experimental groups with n = 8 in each group: sham, IR, AP, and IR + AP. AP (20 mg/kg)was intraperitoneally administered to rats in the AP and IR + AP groups for 30 minutes before 60 minutes of ischemia and followed by 60 minutes of reperfusion. All rats were killed on the same day to evaluate tissue levels of oxidants and antioxidants (catalase, malondialdehyde, myeloperoxidase, superoxidedismutase (SOD), and total glutathione). Results: IR decreased SOD levels in IR group when compared with the sham group. AP supplementation to IR group significantly ameliorated SOD levels (P <.05). Also, IR caused elevation of myeloperoxidase production when compared with the sham group, whereas AP treatment prevented these hazardous effects (P <.05). However, plasma total glutathione, catalase, and malondialdehyde levels did not differ between the AP + IR and the IR rats. Conclusion: The main finding of the present study was that AP may be protective against liver IR injury. Our results suggested that AP pretreatment suppressed oxidative stress and increased antioxidant levels in an rat model of liver IR.