Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin on muscle glucose metabolism that is often under-appreciated is its role to increase muscle perfusion thereby improving insulin and glucose delivery to the myocyte. Either of these responses (myocyte and vascular) may be impaired with insulin resistance, and both impairments occur in type 2 diabetes, resulting in diminished glucose disposal by muscle. There is a growing body of literature suggesting that the loss of microvascular insulin action has important physiological consequences in the early pathogenesis of insulin resistance.