〔Abstract〕 Objective To investigate the role of triptolide-induced down-regulation of cytochrome P450 3 A4(CYP3 A4)expression in causing liver injury. Methods L-02 cells and C57 BL/6 male mice were randomly divided into 4 groups respectively, including normal group(C), triptolide(TP) group, triptolide(TP)+carbamazepine(CBZ) group and triptolide(TP)+amlodipine(AML) group. After 24 h, the medium was collected, and C57 BL/6 male mice were euthanized and taken blood and liver 2 weeks later. The apoptosis rate of each group was detected by flow cytometry, while the damage of mice liver cells was observed by hematoxylin-eosin staining. The kit was uesd to detectethe level of ALT and AST in cell supernatant and mouse serum. The mRNA and protein expression levels of CYP3 A4 in cells and mouse liver were tested by Western blot and RT-PCR. The content of triptolide in cell culture medium and mouse serum was detected by HPLC. Results The results showed that the TP group significantly had more apoptosis and tepatocyte injury than the normal group. However, compared to the TP group, the apoptosis and liver cell injure of the TP+CBZ group significantly relieved, while the TP+AML group aggravated. The levels of ALT and ASTin vitroandin vivoof the TP group were significantly higher than the normal group, and the lower level was observed in the TP+CBZ group and higher level was observed in the TP+AML group. The expression of CYP3 A4 in TP group and TP+AML group significantly declined conapared with group C, while the expression of in the TP+CBZ group significantly higher. The results of HPLC showed that the TP content in the TP+CBZ group was lower than that in the TP group, while it was opposite in the TP+AML group. Conclusion TP can slow down cells metabolism by inhibiting its main metabolic enzyme CYP3 A4, which may be one of the underlying mechanisms of liver damage.