Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei ) is a famous Tibetan medicine for cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl 4 hepatotoxicity. CCl 4 is metabolized via cytochrome P450 (CYP450) to produce reactive metabolites. Whether 70W has any effect on CYP450 is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), HgCl 2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for 7 days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic Aryl hydrocarbon receptor (AhR) and CYP1A2, but HgCl 2 and MeHg increased Cyp1a2 mRNA and CYP1A2 protein levels;70W and Zuotai had no effects on constitutive androstane receptor (CAR) ,CYP2B andCYP2E1 expressions, but HgCl 2 increased CAR and Cyp2b10 mRNA, HgCl 2 and MeHg increased CYP2B and CYP2E1 protein expressions; 70W and mercury compounds had no apparent effects on the expression of pregnane X receptor (PXR) and Cyp3a11 mRNA, as well as CYP3A proteins. 70W and mercury compounds had no apparent effects on the expression of peroxisome proliferator-activated receptor alpha (PPARα) and CYP4A; but HgCl 2 tended to increase Cyp4a10 mRNA and CYP4A protein expressions. 70W and Zuotai had no apparent effects on the expression of farnesoid X receptor (FXR) and Cyp7a1 , while HgCl 2 and MeHg increased CYP7A1 expression. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs, and the effects of 70W and Zuotai on CYP and corresponding nuclear receptors are different from HgCl 2 and MeHg.