Objective: To study the effect and mechanism of compound Tripterygium wilfordii(TW) on attenuating hepatotoxicity through regulation of metabolic enzymes. Method: Sprague dawley (SD) rats were intragastrically administrated with different doses of TW for one month to screen the dose of hepatotoxicity. TW single drug and compound TW were intragastrically administrated for one month respectively. Gene expression changes in rat liver were detected using gene chip technique

and expressions of constitutive androstane receptor (CAR)

pregnane X receptor (PXR)

peroxisome proliferators-activated receptors (PPARs) and aryl hydrocarbon receptor (AhR) were detected using real-time quantitative PCR. Result: Hepatotoxicity dose was 15.6 g·kg-1 of raw TW. Gene chip results showed that TW could inhibit expressions of cytocharome P450 enzymes(CYP) 2E1

CYP8B1 and CYP2B

and induce expression of CYP7A1.Compound TW could induce expressions of CYP3A4

CYP2E1

CYP8B1

and CYP2B. Real-time quantitative PCR results showed that TW could inhibit expressions of nuclear receptors CAR

PXR and PPAR

and Compound TW could improve its inhibitory effect on nuclear receptors. Conclusion: Compound TW preparations can affect expressions of nuclear receptors and metabolic enzymes

which may regulate endogenous and exogenous metabolic processes and thereby attenuate hepatotoxicity.