Objective: To investigated the effect of Huanglian Wendan Tang (HLWDT) on insulin resistance and neurogenesis in hippocampus of diabetic rats. Method: The combined treatment of high-glucose-high-fat diet for 50 days and injection of 35 mg· kg-1 streptozocin (STZ) was used to establish rat type 2 diabetic mellitus model. The successfully modeling rats were selected in the following trial based on blood glucose. Then

the modeling rats were allotted into 6 groups:model group

metformin (0.2 g· kg-1)

berberine (0.2 g· kg-1)

HLWDT (3

6

12 g· kg-1) respectively

and the drugs were given by gavage for 30 days except normal and model groups. Oral glucose tolerance test (OGGT) was performed. The release of insulin (Ins)

expression of insulin receptors (InsR) and β-secretase (BACE1) mRNA were detected in hippocampus neuron. Finally

the number and morphology of neurons were observed by a hematoxylin and eosin (HE) staining of dentate gyrus (DG) region in hippocampus. Result: After treatment of high-glucose-high-fat diet and 35 mg· kg-1 STZ injection

model group rats showed a significantly impaired OGGT (P<0.01)

higher expression of InsR (P<0.01)

lower expression of BACE1 (P<0.05)

compared to the normal rats. The decreased number of neurons in DG region of hippocampus in model group rats was observed. All these adverse changes were reversed by treatment of metformin (0.2 g·kg-1)

berberine (0.2 g· kg-1)

HLWDT (3

6

12 g· kg-1) (P<0.05

P<0.01). Conclusion: Treatment of HLWDT can improve the impaired OGGT and decreased expression of BACE1 mRNA in hippocampus of diabetic rats

as well as the impaired neurogenesis in DG region of hippocampus. The underlie mechanism may be related to increasing expression of InsR mRNA in hippocampus neuron.