Flavonoids, the dominating active ingredient contained in hawthorn extracts, has been widely utilized in various prescriptions of traditional Chinese medicine[1]. However, the effect of them on CYP450 and the pharmacological activity in hyperlipemia rats were still unclear[2], this study assessed the Inhibitory effect of flavonoids on CYP450 in vitro and the therapeutic activity in hyperglycemia rats. The content of some certain flavonoids were simultaneously determined by ultra–performance liquid chromatography electrospray(UPLC–ESI-MS/MS)[3], a sensitive and accurate method established in our laboratory[4],the inhibitory effects of hawthorn extract on CYPs activity were evaluated in rat liver microsomes, and then determined by HPLC based CYPs substrate assay; the SD rats were administrated hawthorn extract mixture for 15 days at a dose of 400mg/kg, then the samples were determined by HPLC. the content of quercetin, catechins, mignonette and puerarin contained in hawthorn extract were 1%,1.2%,1.86% and 1.82%(figure 1)respectively; the high dosage of hawthorn extract can markedly inhibit the metabolism of dextromethorphan(figure 2) and chlorxazone, thus the hawthorn extract can be utilized as a subsidiary hypolipidemic drug. Our study demonstrated that herb-drug interaction should be paid more attention between hawthorn and drug metabolized by CYP2D6 and CYP2E1; the hawthorn had fine hypolipidemic activity, whereas the mechanism was not by effecting the activity of CYP3A2