Fullerenol, a water-soluble C-60-fullerene derivative, has been demonstrated to have the capability to scavenge free radicals in vitro and in vivo. The purpose of this study was to investigate whether fullerenol can scavenge the free radicals that are massively induced during ischemia-reperfusion (UR) injury of the small intestine, either preventively or therapeutically. Clamping the superior mesenteric artery and vein for 60 minutes to induce IIR injury was performed on male mongrel dogs. Thirty dogs were divided into three groups (10 in each): The control (C) group received no medication; the preventive (P) group received fullerenol (1 mg/kg) intravenously 30 minutes before ischemia; the therapeutic (T) group received the same dose of fullerenol immediately after reperfusion. This study was an experimental randomized trial. Intestinal segments were obtained 10, 20, 30, and 60 minutes after reperfusion; and blood samples and specimens of major organs were taken 60 minutes after reperfusion. Concentrations of lipid peroxidation products, including conjugated diene (CD) and malondialdehyde (MDA), and the level of glutathione (GSH) in intestinal tissue were determined. Serum indicators of liver and renal function were measured. Histologic examination of the small intestine and major organs were also performed. A significant increase in intestinal MDA and CD contents was detected at 30 and 60 minutes after reperfusion. The tissue GSH content, in contrast, was decreased 60 minutes after reperfusion. Administration of fullerenol diminished these changes both preventively and therapeutically. Liver and renal functions were within normal limits in all groups. Moreover no obvious histopathologic additional damage could be found in either the P or the T group. It is suggested that fullerenol can be considered a powerful scavenger for the free radicals induced by UR injury of the small intestine.