The majority of patients with macrovascular disease are pre-diabetic or diabetic. Peripheral arterial disease is the most frequent first manifestation of cardiovascular disease in patients with Type 2 Diabetes. Peripheral arterial disease in patients with diabetes develops from an accelerated atherosclerotic process, which occurs at a younger age and is more extensive in patients with diabetes than in those without. Excess glucose levels are an important factor in the genesis of macrovascular disease in diabetes. Chronic hyperglycaemia and accompanying developing relative hyperinsulinemia result in the insensitivity of cells to insulin, leading to the development of insulin resistance. Glucose may affect large vessels via at least three pathways: the glycation process, the activation of protein kinase, and the sorbitol pathway. Exogenous insulin may also have unfavourable effects on the development and progression of atherosclerosis. Endothelial progenitor cells (EPC) have been recognised as performing arterial wall repair, providing an alternative to the local ‘response to injury hypothesis’ for the development of atherosclerotic inflammation. The number and functional capacity of EPCs predict cardiovascular events. Also ,the main pathophysiologic process of atherosclerosis, namely inflammation, is associated with EPC, which influences the progression of macro- and microvascular disease in patients with diabetes mellitus.