Abstract: AIM　To study the effect of 18α-glycyrrhizic acid (18α-GL) on hepatic microsomal drug metabolizing enzymes in rats. METHODS　18α-GL (12.5, 50.0 mg·kg^-1·d^-1) were given ip to male Wistar rats for 3, 6 or 12 consecutive days. The rats were sacrificed 24 h after the last dose and the liver microsomes were prepared for analysis of cytochrome P450 (CYP) isozymes and phase II transferase activites. RESULTS Aniline hydroxylase (CYP2E1) activities in the rats treated with 18α-GL (12.5, 50.0 mg·kg^-1) for 6 days decreased dose-dependently by up to 53.2%; For 3, 6 or 12 days 7-ethoxyresorufin O-deethylase (CYP1A1) activities in the rats of 50 mg·kg^-1 dose group decreased time-dependently by 17.6%, 38.3% and 47.3%, respectively; Erythromycin N-demethylase (CYP3A) activities was significantly inhibited from 23.1% to 34.3%. UDP-glucuronosyltransferase activities toward 7-hydroxy-4-methylcoumarin significantly increased ranging from 19.3% to 29.9%. UDP-glucuronosyltransferase activities toward 4-phenylphenol in the rats treated with 18α-GL (12.5, 50.0 mg·kg^-1) for 6 days increased by 45.9% and 70.3%. Glutathione S-transferase (GST) activities in the rats treated with 18α-GL (12.5，50.0 mg·kg^-1) for 6 days increased by 13.7% and 48.3% in dose-dependent manner. CONCLUSION　18α-GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.