The vasculopathy in diabetes is induced by a proinflammatory thrombotic state which leads to atherosclerosis. The inciting event is insulin-resistance mediated hyperglycemia with clustering of other factors such as hypertension, dyslipidemia, sedentary lifestyle, genetic susceptibility, etc. The detrimental effects of glucose occur even before the threshold of diagnosis of diabetes is attained. This is explained by the phenomenon of “‘glycemic continuum,” i.e. a spectrum of prediabetes to diabetes and cardiovascular disease. Hyperglycemia creates imbalance between nitric oxide (NO) bioavailability and accumulation of reactive oxygen species (ROS) leading to endothelial dysfunction. Treatment of atherosclerosis in diabetes is also discussed in this chapter.