To address the hypothesis that functional changes in tissue transport can be related to structural alterations, we combined mathematical modeling with in vivo experimentation. The model concept includes intersitial diffusion and removal by a distributed microvasculature. Solute and water transport across the peritoneum are measured via a plastic chamber affixed to the abdominal wall of anesthetized SD rats. Solutions containing ¹⁴C mannitol, with or without vasoactive compounds (control (C, n=10), C + nitroprusside (NP, n=10), C + norepinephrine (NE, n=10)), were infused into the chamber, and the volume and tracer concentration were determined over 60 min to calculate the mass transfer coefficient (MTC) and the water flux. At 60 min FITC Dextran (500kd) was given to mark the perfused vasculature. After euthanasia, the tissue under the chamber was frozen, dried, sliced with a cryomicrotome, and examined with fluorescent microscopy and quantitative autoradiography. The microvessel density (x 10³/cm²: NE, 50±10; C, 180±7.0; NP, 225±15) and resulted in marked differences (P<.05) in water flux (µl/min/cm²: NE, 0.1±0.1; C, 1.6±0.4; NP, 1.0±0.2) and in Mannitol MTC (x 10³ cm/min: NE, 0.9±0.3; C, 3.8±0.3; NP, 3.6±0.6). Concentration profiles and calculated capillary permeability and tissue diffusivity were significantly different among the groups. These results demonstrate a direct correlation of mass transfer, diffusion, capillary permeability, and water flux with peritoneal vascular density and validate a method by which mechanistic changes in transport may be measured.