Arterial stiffness has recently been recognized as an important cardiovascular risk marker. Physiological concentrations of insulin diminish wave reflection in the aorta in vivo. This decreases central blood pressure augmentation and augmentation divided by pulse pressure [the augmentation index (AgI)], a measure of arterial stiffness. In the present study, we examined whether a defect in this action of insulin is a feature of insulin resistance and how it relates to other acute actions of insulin, including stimulation of glucose uptake, peripheral blood flow, and autonomic control of heart rate variation. These actions of insulin were quantitated in 50 healthy men (age, 34 +/- 2 yr; body mass index, 27 +/- 1 kg/m2) during 2 sequential insulin infusions, each lasting 120 min (1 and 2 mU/kg x min). Insulin decreased AgI significantly within 30 min, whereas significant increases in peripheral blood flow and normalized low frequency power of heart rate variation, a measure of sympathetic control of heart rate variation, were observed at 150 and 210 min. A blunted decrease in the AgI was significantly associated with a low rate of insulin-stimulated glucose uptake, but not with the other actions of insulin. Insulin action of the AgI was correlated with body mass index and the waist to hip ratio independently of basal AgI, age, and low density lipoprotein cholesterol. We conclude that physiological concentrations of insulin diminish large artery stiffness within 30 min in nondiabetic men. This action precedes insulin action on peripheral vasodilation, heart rate, and autonomic control of heart rate variation. It is correlated with insulin stimulation of glucose uptake and is blunted by known causes of insulin resistance, including overall and abdominal obesity. Resistance of large arteries to insulin-induced decrease in their stiffness is therefore another facet of insulin resistance that could contribute to the association between insulin resistance and cardiovascular disease.