Objective: To investigate the hepatoprotective effect of rapamycin in rats with obstructive jaundice (OJ). Methods: Fifty-four SD rats were equally randomized into sham operation group, OJ model group (model group) and OJ model plus rapamycin treatment group (treatment group). The rat OJ model was established by common bile duct ligation. Rats in treatment group received rapamycin 0.4 mg/kg once daily by subcutaneous injection after operation, and rats in both sham operation group and model group were given normal saline of the same volume instead. Six rats in each group were sacrificed at the postoperative day (POD) 1, 3 and 5 respectively, and the white blood cell (WBC) count, plasma endotoxin (ET) level and liver function parameters were determined, the mRNA expression levels of tumor necrosis factor α (TNF-α) in the liver tissues were measured by RT-PCR and liver pathological changes were also observed. Results: Except for the rats in sham operation group, rats in both model group and treatment group presented overt OJ manifestations, but those of rats in treatment group were milder than those in model group; the WBC count, plasma levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and ET as well as the TNF-α mRNA level in the liver tissue were significantly higher in both model group and treatment group than those in sham operation group at each observation time point (all P<0.05), As shown by pathological studies in the liver specimens from rats in both model group and treatment group, there were pathological changes that included the dilatation of liver sinusoids, hepatocyte necrosis, hyperplastic bile duct cells and inflammatory cell infiltration. The comparison between model group and treatment group showed that all the determined variables were significantly lower in treatment group than those in model group at each observation time point (all P<0.05), and liver pathological damages were also milder in treatment group than those in model group. Conclusion: Rapamycin has hepatoprotective effect in OJ rats, and the mechanism may be partially due to its inhibition of the systemic inflammatory response.