The relationship between diabetic retinopathy and macro-vascular complications in diabetes suggests a pathogenic association between these conditions. Vascular endothelium has been identified as a main site of blood vessel injury in diabetes. Diabetic retinopathy is associated with systemic arterial stiffness and altered vascular endothelium function and structure. Retinal vasculature endothelium at the macula, arterio-venous crossings, and in the optic nerve at the lamina cribrosa region is reported to differ from the endothelium in the rest of the retinal blood vessels. The central retinal artery and vein are in close proximity in the optic nerve where they share a common adventitia; thus, increased arterial wall stiffness and thickness may affect blood flow in the neighboring central retinal vein in this region. Moreover, increased arterial stiffness in small arterial beds is associated with retinal venular widening; it suggests the possibility of central retinal artery compressing the central retinal vein at the lamina cribrosa, thereby compromising venular outflow in the retina of diabetic patients. Altered blood flow in the central retinal vein in the postlaminar region has been detected in patients who experience progression of diabetic retinopathy. Increased hydrostatic pressure in the central retinal vein may play a major role in the pathogenesis of diabetic retinopathy. The aim of this review article is to emphasize this pathogenetic mechanism that has often been overlooked.