Objective: To investigate the effects of erigerontis herba and paeoniae radix rubra formula (Xinshao formula) on the metabolic activity of main subtypes (CYP1a2, CYP2d22, CYP2e1 and CYP3a11) of cytochrome P450s (CYP450) in mice liver and explore its mechanism. Method: Mice were randomly divided into normal group, phenobarbital group (70 mg·kg^-1), and low-, middle-, high-dose Xinshao formula groups (0.31, 0.62, 1.25 g crude drug·kg^-1). After administration, the livers of mice were used to prepare microsomes to determine the metabolic activities of CYP1a2, CYP2d22, CYP2e1 and CYP3a11.The mRNA and protein expression levels of these four CYP450 enzymes and pregnane X receptor (PXR) in liver tissue of mice were evaluated by quantitative real-time polymerase chain reaction (Real-time PCR) and Western blot. The effect of Xinshao formula on the activation of PXR was estimated by reporter gene assay. Result: As compared with the normal group, Xinshao formula could induce the enzyme activity of CYP3a11, up-regulate the mRNA and protein expression levels of CYP3a11 and PXR, and activate PXR (P<0.05,P<0.01). As compared with the model group, middle and high dose Xinshao formula could inhibit CYP1a2 activity (P<0.05), but had no significant effect on the mRNA and protein expression levels of CYP1a2; while Xinshao formula had no significant effects on the activities and the expressions of CYP2e1 and CYP2d22. Conclusion: Xinshao formula could induce enzyme activity of CYP3a11, and the mechanism may be associated with up-regulating PXR expression, activating PXR and promoting CYP3a11 expression. Xinshao formula also could decrease the CYP1a2 activity, but it was not related to regulation of CYP1a2 expression, and the mechanism needs a further study.