Background: Diabetic retinopathy) DR) is a major cause of new-onset blindness among diabetic adults and is characterized by increased vascular permeability, tissue ischemia, and neo-vascularization. Neovascularization of the retina carries a high risk of blindness as a result of vitreous hemorrhage and fibrosis. Vascular Endothelial Growth Factor (VEGF), originally known as vascular permeability factor (VPF), is a signal protein produced by cells that stimulates the formation of blood vessels. Polymorphisms within the VEGF gene lead to differences in VEGF expression between individuals and could influence the etiology of a variety of pathologic conditions with which VEGF has been associated. The aim of this study is to investigate +405G/C polymorphism of VEGF gene in Sudanese patients with type 2 diabetes mellitus (T2DM) and to evaluate its relationship with the development and improvment of diabetic retinopathy. Materials and Methods: A total of 189individuals subjects divided to 3 groups (diabetics with DR, diabetics without DR and health individuals) were observed to determine the relationship between DR and +405 G/C VEGF gene polymorphism. Results: This study revealed that patients with GC genotypes are about 57.6 % at risk (95% CI 1.022-2.431) to develop DR, while the risk is about 40% (95% CI 0.404-0.893) in DM patients without DR than those without GC genotype. Conclusion: These results indicated that +405 VEGF G/C polymorphism could be used in the evaluation, development, and progression of DR.