Diabetes mellitus (DM) is a chronic debilitating disease that affects almost all the systems in the body with accompanying diabetic complications (neuropathy, retinopathy and nephropathy) adding to the global burden of DM. These diabetic complications arise as a manifestation of hyperglycaemic damage induced at the cellular level particularly the endothelial cells (EC). Exposure to hyperglycaemic stress causes endothelial dysfunction, which is the major perpetrator of microvascular disease. Disruption of endothelial function also marks the advent of the subsequent development of cardiovascular disease (CVD) that includes atherosclerosis and coronary artery disease (CAD). Microvascular disease occurs as a result of deficiency of a potent endothelial vasodilator, nitric oxide (NO). NO plays a fundamental role in vascular regulation which is mediated through vasodilation. Other favourable characteristics of NO include antiplatelet activity and prevention of vascular smooth muscle cell (VSMC) proliferation. Unsurprisingly, diminished NO levels in DM will eventually lead to occlusion of the microvasculature in the retina, glomerulus and peripheral nerve (vasa nervorum).