Abstract: OBJECTIVE To study pharmacokinetic profile of cefoselis sulfate in mice plasma and brain with HPLC. METHOD Plasma and brain samples were collected at different time points after caudal vein administration of cefoselis sulfate at single bolus dose of 1 200 mg·kg^-1, HPLC were validated to analysis drug concertations, and pharmacokinetic parameters of plasma and brain were calculated by DAS 3.1 pharmacokinetic program. RESULTS The main pharmacokinetic parameters of cefoselis sulfate in mice blood and brain were: t_1/2 0.202, 0.261 h; K_e 3.424, 2.651; C_max 1984.654, 18.728 μg·mL^-1; AUC_0-t 998.075, 10.119 μg·h·mL^-1; and MRT_0-t 0.904, 1.945 h. CONCLUSION Cefoselis sulfate can quickly distribute in mice brain after caudal vein administration of cefoselis sulfate at single bolus dose, the characteristic of pharmacokinetic profile of cefoselis sulfate between plasma and brain in mice were: they all have close t_1/2, but has longer mean residence time in brain.