Whether insulin influences microvascular exchange is important in understanding its specific role in insulin resistance and the treatment of diabetes. We investigated whether insulin could induce changes in the microvascular flux of albumin from the mesenteric venules of anesthetized male and female Sprague-Dawley rats (n = 11). After catheterization for monitoring of mean arterial pressure (MAP), a loop of small intestine was exteriorized. The mesentery was draped over a coverslip for observation and suffused continuously with bicarbonate-buffered solution (BBS) (pH 7.4, 37 degrees C). After intravenous injection of Alexa 594(TM) labeled bovine serum albumin (BSA, 8 mg/kg), fluorescence intensity (I-f) was recorded on videotape for 30 minutes BBS suffusion and 75 minutes suffusion of BBS plus 0.02 U/ml porcine insulin. Microvascular flux of BSA was measured as a leak index (LI) of I-f in a 10 x 30 mu m window over a postcapillary venule relative to I-f of the adjoining tissue. Insulin induced a rapid 34% decrease in LI within 5 minutes (p < 0.05) that was sustained for the next 30 minutes. We also observed gender and age differences in the permeability response to insulin, as there was a sustained similar to 59% decrease in LI in adult females (n = 5) after 25 minutes, whereas there was an acute, transient (15 min) 45% decrease in LI in juvenile males (n = 6). We conclude that insulin reduces mesenteric venule permeability differently in males and females. Further studies are needed to differentiate the permeability responses with respect to age and gender.