Abstract: To study the enzyme kinetics of schizandrin metabolism in different gender in rat liver microsomes, liver microsomes were prepared from male or female rats. Schizandrin was incubated with rat liver microsomes. Schizandrin and its metabolites were isolated and identified by HPLC-UV method. V_max, K_m and Cl_int of schizandrin in male and female rat liver microsomes were (21.88±2.30) and (0.61±0.07) μmol·L^-1·min^-1·mg^-1(protein), (389.00±46.26) and (72.64±13.61) μmol·L^-1, (0.056 3±0.000 7) and (0.008 4±0.000 8) min·mg^-1(protein), respectively. The major metabolites of schizandrin in female and male rat liver microsomes were 7,8-dihydroxy-schizandrin (M1) and 7,8-dihydroxy-2-demethyl schizandrin (M2b), respectively. Ketoconazole, quinidine, and orphenadrine had different level effects on schizandrin metabolism in both male and female rat liver microsomes, and cimetidine still had some inhibitory effect in male liver microsomes. CYP3A and CYP2C11 may be the main P450 enzymes in schizandrin metabolism and their difference in rat liver microsomes may be the main reason for the sex difference of metabolic enzyme kinetics and metabolites of schizandrin in rats.