Abstract: OBJECTIVE To investigate the effect of the breviscapine combined with lovastatin on the pharmacokinetics of rats in vivo and to reveal the mechanism of the effect of breviscapine on the pharmacokinetics of lovastatin from the perspective of metabolic enzyme. METHODS The concentration of midazolam in liver microsome incubation system was determined by probe drug and HPLC. The effect of breviscapine combined with lovastatin on the activity of CYP3A4 was evaluated. The mRNA expression of CYP3A4 was detected by RT-PCR. And the effect of breviscapine combined with lovastatin on the expression of CYP3A4 protein in rat liver was analyzed at the level of protein translation by Western blotting. RESULTS After the treatment of combination of lovastatin and breviscapine, the plasma concentration of lovastatin in rats increased significantly from 0.39 mg·L^-1 to 1.08 mg·L^-1, clearance decreased from 3.36 L·h^-1·kg^-1 to 1.86 L·h^-1·kg^-1, the drug half-life was extended from 5.0 h to 6.3 h, the AUC of lovastatin after combined administration was 2.43 mg·h·L^-1rose to 4.22 mg·h·L^-1. Compared with the blank group, activity of CYP3A4 did not change significantly in the lovastatin group. Breviscapine group and breviscapine combined with lovastatin group significantly inhibited CYP3A4 activity compared with the blank group; Breviscapine group and breviscapine combined with lovastatin group decreased CYP3A4 enzyme expression significantly compared with the blank group. CYP3A4 enzyme protein content showed that, compared with the blank group, there was no significant change in CYP3A4 enzyme protein content in lovastatin group and breviscapine combined with lovastatin group. CONCLUSION After the combination of lovastatin and breviscapine, breviscapine inhibite CYP3A4 activity by inhibiting the gene transcription level of the enzyme. The combination change the pharmacokinetic process in rats and slow down the metabolism of lovastatin.