Abstract: OBJECTIVE To establish a UPLC detection method for simultaneous determination of mycophenolic acid(MPA) and its glucuronide(MPAG) in plasma of rats, and to investigate gender-related pharmacokinetic characteristics of mycophenolic acid. METHODS Twelve SD rats(half male and half female) were intragastrically administrated with 90 mg·kg^-1·d^-1mycophenolate acetate, and blood was collected from periorbital vein at different time points after administration. Plasma samples were extracted by liquid-liquid extraction and drug concentrations of MPA and metabolite MPAG in plasma were determined using UPLC. The method was developed using Waters BEH C₁₈ column. The gradient elution was performed at a flow rate of 0.35 mL·min^-1 with the mobile phase acetonitrile solution (A)-0.1% formic acid aqueous solution(B). The detection wavelength was at 266 nm and column oven temperature was maintained at 40 ℃. The pharmacokinetic parameters were calculated by using DAS 2.0 software. RESULTS The linear relationship between peak area and concentrations of MPA and MPAG were good in the ranges of 0.31-160 µg·mL^-1(R²=0.999 8) and 0.62-320 µg·mL^-1(R²=0.999 4), respectively. Analytical methods of MPA and MPAG all met the requirements of the methodology. Pharmacokinetic parameters AUC_0-t and C_max of MPA and MPAG in female rats were higher than that in male rats(P<0.05 or P<0.01). In addition, the metabolic rate of genisteinUDP-glucuronosyltransferases(UGT)s substrate and MPA in male rat liver microsomes were significantly faster than that in female rat liver microsomes. CONCLUSION This developed UPLC method is sensitive, accurate and specific, which is suitable to detect the concentrations of MPA and MPAG in the plasma. The pharmacokinetics of MPA and MPAG in rats are gender different, which may be related to the sex difference of UGTs metabolic enzyme activity.