Abstract: OBJECTIVE To investigate the effects of luteolin on activities and mRNA expressions of cytochrome P450 (CYP450) enzymes in rats. METHODS SD rats were randomly divided into test group and control group. After treatment with luteolin or water for 14 d, rats of control group and test group were given the mixture of four probes including phenacetin, bupropion, chlorzoxazone and midazolam. The plasma concentration of probes at a series of time-points after dosing were determined by liquid chromatography tandom mass spectrometry. The activities of CYP450s(CYP1A2, CYP2B1, CYP2E1, CYP3A1) were evaluated according to the pharmacokinetic parameters of corresponding probes. Real-time PCR was applied to assess the mRNA levels of CYP450s. RESULTS The pharmacokinetic parameters of phenacetin, bupropionand and midazolam from test group showed significant differences compared with control group, which indicated that luteolin induced CYP1A2, CYP2B1 and CYP3A1 activities. And no significant difference was found in pharmacokinetic parameters of chlorzoxazone from test group with control group. In addition, treatment with luteolin significantly up-regulated the mRNA expressions of CYP1A2, CYP2B1 and CYP3A1 whereas it had no impact on CYP2E1. CONCLUSION Luteolin can up-regulate the activities and mRNA expressions of CYP1A2, CYP2B1 and CYP3A1.