OBJECTIVE:To study in vivo tissue distribution of genistein-loaded MePEG-PLGA copolymer micelle in mice. METHODS:HPLC method was used to determine the concentrations of genistein in plasma and tissues (heart,liver,spleen, lung, kidney) of mice. The determination was performed on Dikma Diamonsil C18 colunm with mobile phase consisted of methanol-water (60:40,V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 260 nm,and the column temperature was 35 ℃. The sample size was 10 μL. 48 mice were divided into emulsion group and micelle group,with 24 mice in each group. They were given 40 mg/kg genistein emulsion or genistein-loaded MePEG-PLGA copolymer micelle via tail vein. The contents of genistein in plasma and tissues (heart,liver,spleen,lung,kidney) were detected 5,30,90 min after medication. AUC0-90 min and mean residence time(MRT)were compared. RESULTS:The content of genistein in micelle group was higher than emulsion group 5,30,90 min after medication,and the content of genistein in liver tissue was lower than emulsion group 5,30 min after medication. Compared with emulsion group,AUC0-90 min and MRT of genistein in plasma of mice in micelle group were increased significantly(P<0.01);AUC0-90 min and MRT of genistein in liver tissue were decreased significantly(P<0.05). AUC0-90 min of genistein in renal tissue was increased significantly (P<0.05),without statistical significance of other differences (P>0.05). CONCLUSIONS:genistein-loaded MePEG-PLGA copolymer micelle can increase the distribution of genistein in plasma,reduce the distribution of it in liver tissue so as to improve therapeutic efficacy and reduce drug hepatotoxicity.