Objective To investigate the protection on the intrahepatic cholangiocyte mediated by hypoxic preconditioning (HP) after liver transplantation and the role of vascular endothelial growth factor (VEGF). Methods The model of autologous liver transplantation was established, and the rats were divided into 3 groups: autologous liver transplantation group, hypoxic preconditioning before operation group (HP group) and sham operation group. At 6, 12, 24, 48 h after operation, blood samples were collected for examination of the serum total bilirubin (TBIL), direct bilirubin (DBIL) and alkaline phosphatase (ALP), and the expression of VEGF was detected by immunohistochemical method. The pathological changes of cholangiocytes were observed by light microscope. Results As compared with autologous liver transplantation group, the levels of seurm TBIL, DBIL and ALP in HP group were lower (P＜0.05), while the expression of VEGF in HP group was higher at the whole process (P＜0.05). The degrees of billiary epithelium damage and inflammatory infiltration in autologous liver transplantation group were more severe than those in HP group. Conclusion HP has protective effect on cholangiocytes after liver transplantation, in which VEGF may play an important role.