Objective To investigate the protective effect of Yulangsan polysacharide ( YLSPS) and mechanism against ibuprofen-induced liver injury in mice. Methods The mice were randomly divided into the blank control(NC), the model control,YLSPS at 150 mg·kg-1 , 300 mg·kg-1 ,600 mg·kg-1 groups and biphenyldicarboxylate (150 mg·kg-1 BPDC) group. The mice were orally administered with corresponding agents once per day for consecutive 14 days, whereas the blank control group and model control group were orally administered with saline. Except the blank control group, all the other mice were orally administered IBU 200 mg·kg-1 body weight 2 h after last lavagedof medicimes. The mice were fasted and watered ad lib for 20 h after model establishment. Activities of ALT,AST and ALP,content of T-BiL,TNF-α,IL-6 in serum;activities of SOD,GSH-Px and content of MDA in liver tissue were detected. The morphological pathology test was used to examine degrees of hepatic injury. Results Compared with the model control, YLSPS could obviously reduce activities of ALT,AST and ALP,content of T-BiL, MDA,TNF-α and IL-6, and increase SOD,GSH-Px and CAT (P<0. 05), and then lessen the hepatic injury. Conclusion YLSPS showed potential protective effect against ibuprofen-induced liver injury in mice, the mechanism may be related to attenuating free radical injury and inhibiting lipid peroxidation and lowering release of inflammatory factors.