It is well documented that insulin has relevant vasoactive properties. In humans, systemic insulin infusion by the euglycaemic clamp technique causes a dose-dependent increment in peripheral blood flow, suggesting a vasodilatory activity of the hormone. However insulin is not a direct relaxing compound since when it is directly injected into the brachial artery it does not increase forearm blood flow. Therefore it is conceivable that insulin acts as a modulator of vascular reactivity. Both in animals and humans insulin can attenuate the vasoconstrictor effect of adrenergic (noradrenaline, phenylephrine) and non adrenergic (angiotensin II) mediators. Therefore it is now accepted that insulin blunts vasoconstriction by non specific mechanism. Moreover, resistance to this anti-vasoconstrictor effect of the hormone has been hypothesized as a possible mechanism responsible for high blood-pressure values associated with the insulin resistance states. Besides antagonizing vasoconstrictor stimuli, insulin also potentiates vascular relaxation, mainly when induced by endothelium-dependent agonists. In the forearm of normotensive subjects and essential hypertensive patients insulin potentiates the vasodilating effect of acetylcholine, an endothelium-dependent vasodilator. However, while in normotensive subjects the facilitating action of insulin on endothelium-dependent vasodilation is reversed by L-NMMA and therefore involves the nitric-oxide pathway, in essential hypertensive patients it is caused by smooth muscle cell hyperpolarization. In summary, available evidence indicates that insulin-induced vasodilation is probably mediated by indirect mechanisms, including inhibition of contraction due to differrent stimuli and potentiation of endothelium-dependent relaxation. Whether all these vascular effects of insulin are relevant to metabolic and blood-pressure homeostasis remains to be investigated.