Objective: Carpal tunnel syndrome (CTS) is an entrapment neuropathy which is caused by the disruption of blood supply in the median nerve under transverse carpal ligament. Systemic factors facilitate the formation of the syndrome. In this study, neovascularization in the subsynovial tissue and proliferative activity in the stroma are analyzed within the cases of diabetic and idiopathic CTS. Materials and Methods: Subsynovial connective tissue samples of 30 diabetes mellitus patients with CTS and 30 patients with idiopathic CTS were evaluated. Vascular endothelial growth factor (VEGF), CD31, CD34, Factor VIII-related antigen, and smooth muscle actin (SMA) was used to make a comparative study of neovascularization. Proliferative index was assessed using anti-Ki-67 antibody. Results: As a result of the proliferation of endothelial elements, de novo blood vessel formations in the subsynovial tissue were assessed by vascular markers. Significant neovascularization was seen in diabetic group for VEGF, CD31, SMA (P 0.01); and for CD34 (P 0.05) when compared with idiopathic CTS group. In addition, more intense positive staining for CD34, SMA (P 0.01); and for VEGF (P 0.05) was found at isolated stromal cells of diabetic CTS group against idiopathic CTS group. Significantly high proliferative index in subsynovial connective tissue with Ki-67 was observed the diabetic group (P 0.01). Conclusion: VEGF expression has an importance within CTS pathogenesis. Increased ischemia-reperfusion damage, neoangiogenesis, and VEGF expression has an important role frequently CTS occurrence in diabetic patients. Our study supports enhancement in VEGF expression similar to changes in diabetic nephropathy and retinopathy in the neovascularization within the subsynovial connective tissue in the cases of diabetes.