Cerebral cortical microvessels were isolated from bovine brains and incubated in the presence or absence of porcine insulin. The conversion of D-glucose to CO2 and lipids was increased significantly in insulin-treated microvessels. Insulin also caused a significant increase in the activity of cyclic-AMP phosphodiesterase in these microvessels. Specific binding of 125I-insulin to isolated brain microvessels, displaceable by cold insulin was also observed. The effects of insulin reported in this communication mark the first direct evidence that insulin is capable of regulating the metabolic activity of cerebral cortical microvascular tissue. The possible physiological significance of this finding is discussed. © 1982.