Objective: To investigate the protective effect of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion injury (HIRI) in rat and the mechanism. Methods: Twenty male SD rats were equally randomized into sham operation group, TUDCA group, HIRI group and TUDCA plus HIRI group, and underwent sham operation, TUDCA treatment plus sham operation, HIRI model induction, and TUDCA treatment plus HIRI model induction, respectively. TUDCA (250 mg/kg) was administered by gavage 1 h before operation, and HIRI rat model was induced by Pringle maneuver (60-min hepatic ischemia followed by 12-h reperfusion). Rats in each group were sacrificed after 12-h reperfusion and the hepatic samples were collected; the pathological changes in liver tissues were observed, serum alanine aminotransferase (ALT) level was measured, apoptosis of hepatic cells was determined by TUNEL staining, and the proteins associated with endoplasmic reticulum (ER) stress which included glucose regulate protein 78(GRP78), p-eukaryotic translation initiation factor-2α (p-eIF2α) and C-EBP response element binding protein (CHOP) were determined by Western blot analysis. Results: Except in sham operation group and TUDCA group, the liver tissues in either HIRI group or TUDCA plus HIRI group presented the evident pathological changes associated with liver injury, but the degree of injury in TUDCA plus HIRI group was milder than that in HIRI group. Compared with sham operation group, the serum ALT levels, hepatic cell apoptosis and the protein expression levels of GRP78, p-eIF2a and CHOP in liver tissues were significantly increased in both HIRI group and TUDCA plus HIRI group (all P<0.05), but the increasing amplitudes of all these parameters in TUDCA plus HIRI group were significantly less than those in HIRI group (all P<0.05); all the parameters in TUDCA showed no significant alteration (all P>0.05). Conclusion: TUDCA has protective effect against HIRI in rats, and the mechanism may probably be associated with its suppression of ER stress response.