A restricted diffusion model is constructed and solved in order to study the permeability of large adsorbate molecules in the pores of affinity chromatography media, when the adsorbate molecules are adsorbed onto immobilized ligands. The combined effects of steric hindrance at the entrance to the pores and frictional resistance within the pores, as well as the effects of pore size distribution, pore connectivity of the adsorbent, molecular size of adsorbate and ligand, and the fractional saturation of adsorption sites (ligands), are considered. Affinity adsorbents with dilute and high ligand concentrations are examined, and the permeability of the adsorbate in porous networks of connectivity nT is studied by means of effective medium approximation (EMA) numerical solutions. As expected, the permeability of the adsorbate decreases as the size of the adsorbate and/or ligand molecule increases. The permeability also decreases when the fractional saturation of the ligands increases, as well as when the pore connectivity of the network decreases. The dependence of the permeability on the pore connectivity tends to be less marked in adsorbents with concentrated ligand than in porous media with dilute ligand concentration. The conditions are also presented for which the percolation threshold is attained in a number of different systems. The restricted diffusion model and results of this work may be of importance in studies involving the modeling, prediction of the dynamic behavior, design, and control of affinity chromatography (biospecific adsorption) systems employing porous adsorbents. The theoretical results may also have important implications in the selection of a ligand as well as in the selection and construction of an affinity porous matrix, so that the adsorbate of interest can be efficiently separated from a given solution. Furthermore, with appropriate modifications this restricted diffusion model may be used in studies involving the immobilization of ligands or enzymes in porous solids.