Generalized capillary dysfunction is a morbid element in the metabolic syndrome, and it is likely involved in its complications. We tested the hypothesis that vast amounts of serum albumin previously observed in kidneys of rats with the metabolic syndrome were caused, in part, by leakage from renal peritubular capillaries. We report herein large scale leaks of plasma fluid in peritubular capillaries of rats with the metabolic syndrome. This finding was directly demonstrated in vivo, and the presence of leftover albumin residue confirmed the leak in post-mortem kidney specimens. Moreover, renal interstitial fibrosis and tubular atrophy were found in a distribution similar to the leaked renal albumin in obese rats. We suggest that there is an important link between peritubular capillary damage and interstitial fibrosis, represented as tubulo-interstitial disease in the metabolic syndrome. We propose that maintenance of the peritubular microcirculation may improve renal outcomes in diabetes and the metabolic syndrome.