The most common cause of end stage renal disease (ESRD) requiring dialysis is diabetes. Both environmental and genetic factors have been postulated as the risk factors of Diabetic Nephropathy (DN). Hyperglycemia-induced metabolic and hemodynamic pathways are recognized to be mediators of kidney injury. Multiple biochemical pathways have been postulated that explain how hyperglycemia causes tissue damage: Non-enzymatic glycation that generates advanced glycation end products, activation of protein kinase C, acceleration of the polyol pathway and oxidative stress. Three major histologic pathological changes occur in DN: Mesangial expansion, GBM thickening, and glomerular sclerosis. It now seems clear in targeting a therapeutic regimen to achieve blood glucose, blood pressure and proteunuric goals, dietary protein and salt restriction, weight reduction, aggressive lipid lowering, smoking cessation and exercise. Multiple intensive interventions reduce cardiovascular events as well as nephropathy by about half when compared with conventional multifactorial treatment.