OBJECTIVE： To study the effects of high-mobility group box 1 protein （HMGB1）-mediated inflammatory pathway HMGB1-Toll like receptor 4 （TLR4）/nuclear transcription factor κB（NF-κB）on liver injury of rats induced by Tripterygium wilfordii， and to provide reference for clarify the mechanism of liver injury induced by T. wilfordii. METHODS： Totally 24 SD rats were randomly divided into blank group （normal saline， i.g.）， T. wilfordii group （16 g/kg by crude drug， i.g.） and neutralizer group （16 g/kg T. wilfordii crude drug i.g. after i.p injection of 100 mg/kg Ammonium glycyrrhizinate solution 3 h）， with 8 rats in each group. All rats were treated for consecutive 3 weeks. The serum levels of AST and ALT in rats were detected every week. After the end of medication， the serum levels of HMGB1， IL-1β， IL-2 and TNF-α were detected by ELISA method； the protein expression of HMGB1， NF-κB p65 and TLR4 in liver tissue of rats were detected by Western blot assay. The pathological changes of liver tissue in rats were measured with HE staining method. RESULTS： After 3 weeks of treatment， the serum levels of AST， ALT， HMGB1， IL-1β， IL-2 and TNF-α in rats， the protein expression of HMGB1， NF-κB p65 and TLR4 in liver tissue of rats in T. wilfordii group were significantly higher than blank group and neutralizer group （P＜0.05 or P＜0.01）. Hepatocyte edema was found around the central vein of the liver， and circular vacuoles were seen in some hepatic cytoplasm in T. wilfordii group； only varying size of vacuoles were found in a small number of cells in neutralizer group. CONCLUSIONS： T. wilfordii induced liver injury may be associated with the activation of HMGB1-TLR4/NF-κB inflammation pathway.