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Objective: To study the changes of endothelin (ET), tumor necrosis factor-α (TNF-α) before and after puerarin treatment in patients with diabetes mellitus vascular complications (DMVC). Methods: Ninety-eight DMVC patients were divided into 2 groups, they were given puerarin (n=68) and normal saline (n=30) respectively, 20 diabetic patients without vascular complications (NDMVC) were taken as control, who were also given puerarin. All the patients were treated on the basis of controlling blood glucose. Plasma ET and serum TNF-α were determined by radioimmunoassay (RIA) before and after treatment. Results: Plasma ET and serum TNF-α in DMVC got higher than that of NDMVC patients (P<0.05), and ET level was correlated with TNF-α (r=0.69, r=0.73, P<0.01). After treatment, the levels of ET and TNF-α were significantly lower than those before treatment of DMVC patients with puerarin (P<0.05). Conclusion: Puerarin could regulate the levels of plasma ET and serum TNF-α of DMVC patients, suggesting that it has the function of regulating endothelial cells.