Insulin resistance plays a key role in the pathogenesis of type 2 diabetes and precedes the onset of diabetes. Skeletal muscle is the major site for insulin-mediated glucose storage and is thereby a key influence on postprandial blood glucose levels [1]. Insulin resistance is characterised by impaired insulin-mediated glucose disposal in skeletal muscle and is often associated with endothelial dysfunction. Although multiple mechanisms underlie development of insulin resistance, our research over the past 15 years implicates microvascular dysfunction in skeletal muscle as a major cause. We have shown that insulin enhances flow to the microvasculature in muscle facilitating access of glucose and insulin to the myocyte, thus contributing to enhanced glucose disposal [2]. Obesity [3], insulin resistance (induced by high fat or high sodium diets for example) [4] and ageing [5] are associated with impaired microvascular responses in skeletal muscle. Impairments in insulin-mediated microvascular perfusion in muscle can directly cause insulin resistance [6], and this event occurs early in the aetiology of this condition. Understanding the mechanisms involved in the development of microvascular dysfunction in muscle is crucial to prevent the progression of insulin resistance, and it also provides a novel treatment strategy in which microvascular function can be targeted preventing the development of type 2 diabetes.