Few studies have pointed out the relationship between ischemia-reperfusion (IR) injury and the coagulation system. Antithrombin III (AT) has anti-inflammatory effects in IR injury. We investigated the effect of AT supplementation on renal IR injury in rats achieved by clamping of the left renal pedicle for 60 min and subsequent 24-h reperfusion after right nephrectomy. Sprague-Dawley rats were divided into three groups: sham-operated (no IR injury), ischemic controls, and an AT-treated group (250 U/kg before reperfusion). Creatinine values, tissue malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and histopathological damage were investigated after 24 h of reperfusion. In addition, the 7-day survival rates in each group were evaluated. Creatinine and MDA levels and MPO activity were significantly elevated and histopathological damage was more severe in controls than ill the sham group (P < 0.05). Creatinine and MDA levels and MPO activity were significantly lower and there was less histopathological damage in the AT group than in controls. Accumulation of lipid peroxidation products and neutrophils were significantly inhibited by AT treatment. We conclude that AT may attenuate renal IR injury in rats.