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Diabetes mellitus (DM) is a metabolic disorder which is characterized by inappropriate hyperglycemia. It is becoming an epidemic disease in developing countries. Diabetic patients are frequently afflicted with a vascular dysfunction and wound healing defect. In spite of intense investigations, over the past 2-3 decades, optimal treatment options and related mechanisms are still unclear. MicroRNAs (miRNAs) are small noncoding RNAs considered as regulators of a vast number of biological processes including endothelial cell function controlling molecular signaling pathways in diabetic pathogenesis. Down regulation of microRNA-126 (miR-126) which may regulate angiogenesis and vascular integrity plays a significant role in the pathogenesis and complications of DM. This paper discusses the potential application of miR-126 as a novel therapeutic agent capable of reducing diabetic vascular complications in different types of DM based on the up-to-date reports.