Objective To investigate the protective effects of Codonopsis lanceolata saponin (CLS) on hepatic ischemia-reperfusion injury (HIRI) and its mechanism in rats.Methods The rats were divided randomly into 3 groups:sham-operated (SO) group, HIRI group and CLS group.HIRI model was made by Pringle method.CLS group was pretreated with CLS (200 mg · kg-1 · d-1) by intragastric administration for 7 days before operation, while SO group and HIRI group were given with distilled water 10 ml · kg-1 · d-1 for 7 days.ALT, AST, SOD, MDA in serum, and SOD and MDA in hepatic tissue were detected by colorimetric method.IL-18 in serum and hepatic tissue was detected by ELISA.Results The levels of serum ALT, AST, MDA, IL-18, TNF-α and tissue MDA, IL-18 in HIRI group were significantly higher than those in SO group and CLS group (all P < 0.05), respectively.The serum and hepatic tissue SOD activity in HIRI group was significantly lower than that in SO group and CLS group (all P < 0.05).Histological observation revealed that the obvious cell necrotic foci with a large number of inflammatory cells infiltration in the HIRI group, while the lesion was obviously alleviated in CLS group.Conclusions Codonopsis lanceolata saponin preconditioning alleviates hepatic ischemia/reperfusion injury.The mechanism may be correlated with inhibiting inflammatory factors and enhancing anti-oxidation.