OBJECTIVE： To investigate the protective effect and mechanism of neferine on hepatic ischemia/reperfusion （I/R） injury in mice. METHODS： Totally 40 mice were randomly divided into sham operation group （normal saline）， model group （normal saline）， and neferine low-dose， middle-dose and high-dose groups （10， 30， 60 mg/kg）， with 8 mice in each group. They were given relevant medicine intragastrically once a day for consecutive 7 d. After medication， except for sham operation group， mice in other groups were given occlusion of liver pedicle 60 min and then given perfusion for 6 h to induce hepatic I/R injury model. After modeling， the levels of ALT， AST， TNF-α and IL-6 were detected. The pathological change of hepatic tissue was observed after HE staining and the inflammation was scored. The levels of MDA， SOD， TNF-α mRNA and IL-6 mRNA， and the protein expression level of NF-κB p65 in hepatic tissue were determined. RESULTS： Compared with sham operation group， serum levels of ALT， AST， TNF-α and IL-6， levels of MDA， SOD， TNF-α mRNA and IL-6 mRNA and the protein expression level of NF-κB p65 in hepatic tissue were increased significantly in model group （P＜0.05）. There was a large number of inflammatory cells infiltration and hepatic cells necrosis， and the inflammation score increased significantly （P＜0.05）. Compared with model group， except that serum levels of ALT and TNF-α， levels of TNF-α mRNA and MDA， protein expression level of NF-κB p65 and inflammation score of hepatic tissue were not significantly reduced in neferine low-dose group， above indexes of other groups were decreased significantly （P＜0.05）. In neferine middle-dose and high-dose groups， the structure of hepatic lobules was complete， the morphology of hepatocytes was normal， and pathological injury had been significantly improved. CONCLUSIONS： Neferine shows protective effect on hepatic I/R injury model mice in dose-dependent manner， the mechanism of which may be associated with reducing oxidative stress， inhibiting inflammatory reaction and reducing the protein expression of NF-κB p65 in hepatic tissue.