Objective:To elucidate the role of ERK1/2 MAPKs signal transduction in the protective effects of ischemic preconditioning during liver transplantation. Methods: Twenty-four rats were equally randomized into 4 groups: sham control (group A); liver transplantation (group B); ischemic preconditioning+liver transplantation (group C), and MEK inhibitor intervention+ischemic preconditioning+liver transplantation (group D). Serum AST and ALT were detected after operation and cellular ultrastructures were observed by transmission electron microscopy. Liver tissue ERK1/2 MAPKs phosphorylation activities were evaluated through determining ERK-1 protein phosphorylation by Western blotting. Results: Serum ALT and AST activity in group B and group D was significantly higher than those in group A, and remained normal in group C. Liver tissue ERK1/2 MAPKs phosphorylation activity increased significantly in group C, and the activation effect was inhibited in group B and D. Cellular ultrastructure was obviously damaged in group B and group D, and the damage was prevented in group C.Conclusion: Ischemic preconditioning has a protective effect on transplanted liver cells in which ERK1/2 MAPKs pathway plays a pivotal role.