Abstract: OBJECTIVE To evaluate the effect of Lycoris radiata on cytochrome P450 enzyme activity using the cocktail method. METHODS Rats were randomly divided into three groups:the control group, low and high dose of Lycoris radiata group. The control group was given physiological saline, and the rats in the low and high dose of Lycoris radiata group were intragastrically administrated 0.5, 1.0 g·kg^-1 of Lycoris radiata for 15 d. Then on the 16th day, probe drugs were administrated by gavage, and the concentration of probe drugs was determined by UPLC-MS/MS. RESULTS Compared with the control group, the AUC_(0-t) and C_max of bupropion in the low and high dose of Lycoris radiata group increased(P<0.05) and the CL_z/F decreased(P<0.05). Compared with the control group, the AUC_(0-t) of metoprolol, midazolam, and phenacetin in the high dose Lycoris radiata group decreased(P<0.05), and CL_z/F increased(P<0.05), while there was no statistical difference between the low dose Lycoris radiata group and the control group. Compared with the control group, the AUC_(0-t)and CL_z/F of tolbutamide in the Lycoris radiata group were not statistically different, but the C_max of the Lycoris radiata group decreased(P<0.05). CONCLUSION Lycoris radiata can inhibit CYP2B1 enzyme activity in rats, induce CYP2D1, CYP3A2 and CYP1A2 enzyme activities in rats, and slightly induce CYP2C11 enzyme activity in rats.