Abstract: OBJECTIVE To study the inhibitive and inductive effect of furanodiene (FDE) on main cytochrome P450 isoforms(CYPs) in rat and human liver microsomes. METHODS Probe substrate method was used to evaluate the in vitro inhibitory effect of FDE on CYP1A, CYP2A, CYP3A, CYP2C, CYP2D and CYP2E1 in rat and human liver microsomes. Rats were administered with FDE at a dosage of 40 mg·kg^-1 or 160 mg·kg^-1 by gastric lavage for successive 7 days, then the metabolic activities of main CYPs in liver microsomes were evaluated by cocktail-LC-MS/MS method. The inductive effect of FDE was evaluated by comparing the activities of main CYP450 isoforms in rat liver microsomes with or without treatment of FDE. RESULTS FDE inhibited the activities of CYP2D1 and CYP2C6/7 in rat liver microsomes, with the IC50 values of 15.8 and 23.8 μmol·L^-1, respectively. FDE also inhibited CYP2C9 activity in human liver microsomes with the IC50 of 26.1 μmol·L^-1. Compared with the vehicle group, 40 mg·kg^-1 FDE did not obviously change the activities of main CYPs in rat microsomes, while 160 mg·kg^-1 of FDE increased the activity of CYP2E1 to 164% of the vehicle group. CONCLUSION FDE has a negligible or weak inhibitory effect on main CYP450 in rat and human liver microsomes, FDE can not induce main CYP450 in rat liver microsomes at 40 mg·kg^-1 while induce CYP2E1 to some extent at 160 mg·kg^-1.