We recently showed that, in conscious rats, acute infusions of insulin (10-15 fold increase in plasma insulin) produced decreases in hindquarter vascular resistance, but only if, changes in sympathetic outflow were prevented with a ganglionic blocker. The aim of the present investigation was to determine if similar effects of insulin could be observed in a preparation that allowed direct visualization of striated muscle (cremaster) microvessels. Initial studies with topical application of insulin showed that third-order arterioles (A3), but not first- or second-order arterioles vasodilated in response to 800 microU/ml and 8 mU/ml of insulin. Systemic (euglycemic) infusion of insulin (6 mU/ml, but not 2 mU/ml) also increased A3 arteriole diameter in animals treated with a ganglionic blocker, but not in control rats. These data show that insulin can have a direct vasodilator effect on striated muscle microvessels if concomitant increases in sympathetic outflow are absent. However, the response was only present with supraphysiological doses of the hormone.