Objective:To investigate the protective effect of sinomenine on the cold ischemia/reperfusion injury during orthotopic liver transplantation (OLT) in rats.Methods: OLT were performed in normal rats using Kamada’s two-cuff technique.The rats were randomly divided into sham operation,control and two sinomenine groups.Animals in sinomenine groups were treated with low (40 mg/kg) or high dose (80 mg/kg) of sinomenine.The serum and tissue samples of rats in each group were collected 2,6,12, and 24 h after reperfusion,and the one-week survival rate was observed.The apoptosis index (AI) of liver cells after OLT was detected by TUNEL.The expression of TNF-α and IL-1β mRNA in the liver were detected by RT-PCR.Results: Compared with the control group,the level of ALT was significantly decreased in the two sinomenine treatment groups at different time points after transplantation,and their one-week survival rates were also significantly increased (75%,75% vs 12.5%,P<0.01).Compared with the control group,the AI of liver cells was markedly decreased in sinomenine treatment groups (P<0.01).Sinomenine treatment also significantly decreased the expression of TNF-α and IL-1β mRNA (P<0.01) and greatly ameliorated the focal necrosis of hepatocytes and sinusoidal endothelial cells (SECs).Conclusion: Sinomenine can inhibit hepatocyte apoptosis by inhibiting the synthesis of TNF-α and IL-1β.sinomenine can prevent hepatic cells and SECs from cold ischemia/reperfusion injury during orthotopic liver transplantation in rats.