Abstract: OBJECTIVE To compare the pharmacokinetic differences of metformin hydrochloride between normal and diabetic rats. METHODS Metformin hydrochloride was orally administrated to the normal and diabetic rats. The blood samples were collected at different time. The concentration of metformin hydrochloride in plasma was determined by HPLC method. The software of DAS1.0 was used to estimate the pharmacokinetic parameters. RESULTS The main pharmacokinetic parameters of metformin hydrochloride in normal and diabetic rats were Cmax=9.41 μg·mL-1, t1/2=161.8 min, Cl/F=0.079 L·min-1·kg-1 and Cmax=20.09 μg·mL-1, t1/2 =1 718.93 min, Cl/F=0.012 L·min-1·kg-1, respectively. CONCLUSION The main pharmacokinetic parameters of metformin hydrochloride in normal and diabetic rats have significant differences (P<0.05)