We investigated the effect of insulin on the vascular reactivity to noradrenaline, serotonin and potassium chloride in rat mesenteric resistance arterioles in vitro. Mesenteric artery segments were placed in a myograph system. Sensitivity to noradrenaline, serotonin and KCl was tested after an equilibration at 37-degrees-C. Thereafter, arteries were incubated with buffer alone or with insulin (40, 100, 250 and 400 mU/ml) for one hour at 37-degrees-C. Sensitivity to the three vasoconstrictors was retested. Incubation with noradrenaline, serotonin and KCl resulted in a dose dependent increase in wall force. Exposure with buffer did not change the shape of the dose-response-curve. The same was true for the lowest dose of insulin (40 mU/ml). However, incubation with insulin at concentrations of 100, 250 and 400 mU/ml led to a reduction in wall force by 37-77 %. The reduction in the slope of the curve and the maximal response suggest a non-competitive inhibition. Supraphysiological doses of insulin attenuate the vasoconstriction by noradrenaline, serotonin and KCl in rat mesenteric arteries in vitro.