Impaired insulin transcapillary transport and the subsequent decrease in insulin delivery to target organs have been suggested to play a role in insulin resistance. These defects were studied in fructose-fed rats, an animal model with insulin resistance. For this study, male Sprague-Dawley rats were fed with either a 60% fructose enriched (F) or a standard chow diet (N) for a total of 2, 4, or 8 weeks. Capillary permeability to albumin was assessed at the end of each dietary period by quantifying the extravasation of albumin-bound Evans blue (EB) dye in different organs. Unanesthetized animals were injected with Evans blue dye (20 mg/kg) in the caudal vein 10 min before being killed and EB dye was extracted by formamide from selected organs collected after exsanguination. As expected, rats had an increase in blood pressure upon feeding with fructose at 4 and 8 weeks (F, 149 +/- 3 mm Hg; N, 139 +/- 3 mm Hg; P < .05). Using this technique, we showed a 56% and a 51% reduction in capillary permeability in skeletal muscles at 4 and 8 weeks of fructose feeding, respectively (4 weeks: N, 44.5 +/- 5.0 microg/g of dry tissue; F, 19.8 +/- 4.2 microg/g of dry tissue; P < .01 and 8 weeks: N, 23.3 +/- 3.7 microg/g of dry tissue; F, 11.3 +/- 4.0 microg/g of dry tissue; P < .05). Similar changes were observed at 4 weeks in the thoracic aorta (N, 82.8 +/- 8.8 microg/g of dry tissue; F, 53.0 +/- 5.1 microg/g of dry tissue; P < .02) and skin (N, 36.0 +/- 5.3 microg of dry tissue; F, 15.0 +/- 2.3 microg/g of dry tissue; P < .02) and at 8 weeks in the liver (N, 107.5 +/- 4.3 microg/g of dry tissue; F, 80.9 +/- 3.2 microg/g of dry tissue; P < .01). In conclusion, fructose feeding is accompanied by a significant and selective reduction of Evans blue leakage primarily in skeletal muscle and liver, and transiently in the skin and aorta, consistent with a role for decreased tissue insulin delivery in insulin resistance.