Abstract: This study was designed to compare normal and diabetic rats in the pharmacokinetic and tissue distribution of honokiol and its metabolites. Type 2 diabetic rat model was established using high-fat diet feeding for 6 weeks followed by single intraperitoneal injection of low dose (30 mg·kg^-1) strepotozotocin. The concentration of honokiol and its metabolites were determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated using DAS 3.0 software. The C_max of honokiol in the normal rats and diabetic rats are 872.5 ±233.1 and 614.7 ±182.4 μg·L^-1 respectively (P < 0.05), and the AUC are 3 827.2 ±926.9 and 3 004.7 ±391.4 μg·h·L^-1 respectively. Meanwhile, AUC_0-t and C_max of the metabolite M2 were significantly increased in diabetic rats. The concentrations of honokiol in liver, kidney and brain in the diabetic model group were higher than those of the normal control group. Meanwhile, the exposure of M1 in liver, M2 in liver and kidney of the model group were higher than that in the normal group. The data suggest that the pharmacokinetics and tissue distribution of honokiol and its metabolites are changed in the pathological state of diabetes.