Vascular integrity in the healthy endothelium is maintained through the release of a variety of paracrine factors such as NO (nitric oxide). Endothelial dysfunction, characterized by reduced NO bioavailability, is associated with obesity, insulin resistance and Type II diabetes. Insulin has been demonstrated to have direct effects on the endothelium to increase NO bioavailability. Therefore altered insulin signalling in the endothelium represents a candidate mechanism underlying the association between insulin resistance and endothelial dysfunction. In recent years, it has become apparent that insulin sensitivity is regulated by the adipocytokines, a group of bioactive proteins secreted by adipose tissue. Secretion of adipocytokines is altered in obese individuals and there is increasing evidence that the adipocytokines have direct effects on the vascular endothelium. A number of current antidiabetic strategies have been demonstrated to have beneficial effects on endothelial function and to alter adipocytokine concentrations in addition to their effects on glucose homoeostasis. In this review we will explore the notion that the association between insulin resistance and endothelial dysfunction is accounted for by adipocytokine action on the endothelium. In addition, we examine the effects of weight loss, exercise and antidiabetic drugs on adipocytokine availability and endothelial function.