Renal microvascular disease reflected directly by peritubular capillary flow reduction and indirectly by renal function impairment has been documented in early diabetic nephropathy (DN) associated with normoalbuminuria and normal serum creatinine concentration. The renal microvascular disease observed in early DN [chronic kidney disease (CKD) stages 1-2] could progress under current practice to late DN (CKD stages 3-5) with a further reduction in peritubular capillary flow. This advanced renal microvascular disease in late DN is characterized by therapeutic resistance to vasodilators and altered vascular homeostasis associated with impaired nitric oxide production. The renal microvascular disease is progressive as the disease severity progresses and eventually induces chronic renal ischemia and a progressive tubulointerstitial fibrosis. Further study has revealed that early DN is associated with an adequately functional vascular homeostasis. Therefore, recognition and treatment of early renal microvascular disease at early DN (stages 1-2) could enhance renal perfusion and restore renal function.