Abstract: Objective: To study the protective effect of tiopronin and splenectomy on the hepatic ischemia reperfusion injury in rats,and to investigate its mechanism.Methods: Ninety male Wistar rats were divided into sham operation group,ischemia-reperfusion(IR) group,tiopronin group,splenectomy group and tiopronin+splenectomy group.The hepatic artery and portal vein to the left and median liver lobes were occluded;the levels of serum alanine amintransperase(ALT),superoxide dismutase(SOD),malondialdehyde(MDA) and the pathological variation were observed;the necrosis of the hepatocyte and the infiltration of neutrophilic granulocytes were determined by HE staining.Results: The levels of ALT and MDA in serum in IR group was significant higher than that in the sham group(P<0.01);the levels of ALT and MDA in tiopronin group and splenectomy group were significantly lower than that in IR group(P<0.01),and the level of ALT and MDA in tiopronin + splenectomy group were significantly lower than that in IR group,tiopronin group and splenectomy group(P<0.01).The level of SOD in serum in tiopronin + splenectomy group was significantly higher than that in IR,tiopronin and splenectomy group(P<0.01),and the difference was significant between IR group and tiopronin groups(P<0.01);histological lesion of the liver was observed in IR group,and there was an obvious increase of neutrophilic granulocytes(P<0.01);the necrosis of the liver and the number of neutrophilic granulocytes in tiopronin group and splenectomy groups were significantly lower than those in IR group(P<0.05 to P<0.01).Conclusions: Tiopronin can increase the activity of SOD,decrease the level of MDA and protect the liver from ischemia reperfusion injury in rats,and splenectomy has the same function as tiopronin.The combined therapy of tiopronin and splenectomy may enhance the protective effect on the hepatic ischemia reperfusion injury in rats.