Objective: To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus (T2DM) rats and the effects of Panax Quinquefolius Saponin (PQS) of stem and leaf. Methods: The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg) plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose (SHG) group and fluctuant high blood glucose (FHG) group according to fasting blood glucose coefficient of variation (FBG-CV), and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose: PQS 30 mg/(kg·d) group, PQS 60 mg/(kg·d) group, metformin hydrochloride control (MHC) group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control (NOR) group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor (HGF), and serum nitric oxide (NO), endothelin-1 (ET-1), tumor necrosis factor α (TNF-α), and soluble intercellular adhesion molecule 1 (slCAM-1) were measured. Results: In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased (P〈0.01); in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further (P〈0.01 or P〈0.05); meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly (P〈0.01). However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion: Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothel