Objective To compare the protective effect of ischemic preconditioning(IP) and caspase inhibitor on ischemia reperfusion(IR) injury of the liver in rats,and to investigate the possible mechanism. Methods SD rats subjected to 60 or 120 minutes of 70% hepatic ischemia and 3 hours of reperfusion,respectively,then divided randomly into 6 groups: (1)Ischemia/ reperfusion group 1 (IR 1 group);(2)IR 2 group;(3)Ischemia preconditioning group 1(IP 1 group);(4)IP 2 group; (5)Caspase inhibitor treatment group1(T 1 group);(6)T 2 group.Serum levels of aspartate aminotransferase (AST) and alanine aminotransfernase (ALT),and liver Caspase-3 activity, hepatocytes apoptosis,and animal seven-day(7 d) survive rate were determined. Results Both ischemic preconditioning and Caspase inhibitor treatment could protect the liver against IR injury,and their protective effect in IP 1 group and T 1 group was equally at 3h reperfusion after 60min ischemia. At 3h reperfusion after 120min ischemia, the effect of inhibiting Caspase-3 activity and decreasing hepatocyte apoptosis in T 2 group were significantly superior to those in IP 2 group(P0.05). Conclusions Both IP and Caspase inhibitor treatment can protect the liver against IR injury in rats,and the protective effect is no significant difference between the two methods.However IP is more simple?safe and cheaper comparing with Caspase inhibitor treatment.