Objective: To investigate the protective effect of ulinastatin on the liver grafts in rats with orthotopic liver transplantation and tis mechanism. Methods: The livers removed from the donors were respectively perfused with UW solution alone (model group) or UW solution containing ulinastatin (ulinastatin group), heme oxygenase 1 (HO-1 group) inducer CoPP (CoPP group) or HO-1 inhibitor ZnPP (ZnPP group), with perfusate reservoired for 1 h, and then were orthotopically transplanted into the recipient rats. The liver grafts and blood samples were harvested from the recipient rats at 24 h after transplantation, the pathological examination and scoring for the liver was performed, the HO-1 mRNA and protein expressions in the liver grafts were determined by real-time PCR and Western bolt respectively, and the serum levels of IL-2 and IL-10 were detected by Elisa assay. Results: Compared with model group, the injuries in the liver grafts were remarkably alleviated and Suzuki scores were significantly decreased in ulinastatin group and CoPP group, while the liver injury was aggravated and Suzuki score was significantly increased in ZnPP group (all P<0.05); the HO-1 mRNA and protein expressions in the liver grafts were significantly up-regulated in ulinastatin group and CoPP group, but were significantly down-regulated in ZnPP group (all P<0.05); the IL-2 levels were decreased and IL-10 levels were increased significantly in ulinastatin group and CoPP group, while the IL-2 level was increased and IL-10 level was decreased significantly in ZnPP group (all P<0.05). Conclusion: The protective effect of ulinastatin on the liver grafts in rats may probably be associated with its up-regulating HO-1 expression and thereby reducing the reperfusion injury and inhibiting the rejection reaction.