Our previous studies have investigated the effects of exercise intervention on vascular endothelium functions and the endocrinological change of endothelium-dependent vasodilation in the middle-aged patients with Impaired Glucose Tolerance (IGT). The present study was aimed to explore the endocrine mechanism of the endothelium-dependent vasodilation by examining the changes of leptin, resistin, adiponectin and Free Fatty Acid (FFA) in the IGT patients after exercise intervention. Exercise intervention decreased leptin, resistin and FFA significantly, but increased adiponectin. Furthermore, correlations were identified between vascular endothelium function items and leptin, adiponectin and FFA. Exercise intervention may improve vascular endothelium-dependent dysfunction through decreasing leptin and FFA, and increasing adiponectin in middle-aged patients with IGT. This present study provided the direct clinical data supporting the implementation of exercise intervention to prevent diabetes mellitus during the early stages.