Abstract: Objective To explore the effect of P-glycoprotein (P-gp) or breast cancer-resistance protein (BCRP) on the distribution of fluconazole in rat brain. Methods Sprague–Dawley rats (n=18) were divided into 3 groups randomly with group A (n=6)receiving an intravenous injection of 20 mg/kg fiuconazole, rats in group B (n=6) receiving 20 mg/kg fiuconazole and 5 mg/kg P-gp inhibitor verapamil, rats in group C (n=6) receiving 20 mg/kg fiuconazole and 40 mg/kg BCRP inhibitor pantoprazole, respectively.Microdialysis probes were implanted into the SD rats' striatums to collect their brain extracellular fiuid (ECF) continuously after the intravenous injection of fiuconazole, and the fiuconazole concentrations in the blood and brain ECF were measured using highperformance liquid chromatography (HPLC) technique.Then, the penetration rate of fiuconazole into the blood-brain barrier (BBB)was compared between treatment groups (Group B or C) and control group (Group A) to estimate the effect of P-gp and BCRP on the distribution of fiuconazole. Results Penetration rate in group B was 81.4%±15.5%, signi ficantly higher than 62.7%±12.4% in group A and 63.0%±12.1% in group C (P＜ 0.05, respectively) with no significant difference in the latter two groups. Conclusion P-gp at the BBB impedes the in fiux of fiuconazole into the brain, and its inhibitor can increase the penetration rate of fiuconazole into BBB, while the BCRP does not involved in transporting fiuconazole between blood and brain.