Abstract: This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, C_max of metformin was significantly decreased (P<0.01) and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO group; t_1/2 was significantly decreased in the METF+PRAV group; C_max was significantly decreased and MRT_0-t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT_0-t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, C_max of metformin was significantly decreased (P<0.01), and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.