The extravascular matrix is believed to carry negative charge due to its glycosaminoglycans (GAGs) composition. In the present study, we developed an electrodiffusion-convection model to investigate the mechanisms by which this negative charge affects the charged molecule transport through the interstitial space. The model predictions demonstrate that the apparent tissue diffusion coefficient of negatively charged albumin (net charge = -19) in rat mesentery should be comparable to that of neutral dextran with equivalent hydrodynamic radius. The discrepancy in their concentration distributions in the mesenteric tissue, which was observed by Fox and Wayland, may be explained by the charge effect of the tissue matrix, especially by the partitioning between the vascular and extravascular compartments, instead of different apparent diffusion coefficients. The charge effect induces equivalent to about two-fold difference in apparent tissue diffusion coefficients of charged albumin and neutral dextran with same free diffusion coefficients. Furthermore, our results indicate that the more negative charge the interstitium has, the smaller the interstitial fluid flow is when the same tissue-lymph pressure gradient is applied