Abstract: OBJECTIVE To investigate the effects of simvastatin (SV) on drug-metabolizing enzyme of liver microsome in rats. METHODS Rats were given SV by oral administration，qd 7. Liver microsome was prepareded by ultracentrifugation. Cytochrome P450 (CYP) content was determined by CO-difference spectrum. Erythromycin, aniline, 1-chloro-2, 4-dinitrobenzene (CDNB), ethacrynic acid, 7-hydroxy-4-methylcoumarin and 4-Hydroxybiphenol were used as the substrates for the determination of CYP3A4，CYP2E1, glutathione S transferase(GST) and πGST, uridine diphosphoglucuronyl transferase (UGT1 and UGT2) activities. RESULTS After SV oral administration, CYP content and CYP3A4 activity were significantly decreased in rats, but no difference of CYP2E1 activity was found. Meanwhile, SV administration caused a remarkable increase in liver microsome GST, πGST, UGT1 and UGT2 activities. CONCLUSION SV increased in CYP3A4 activity and reduced Ⅱ phase drug-metabolized enzyme in rats.