A model derived from fiber matrix theory to predict the permeability of the eye＇s fibrous tissues, namely the sclera and corneal stroma, to water and solutes ranging from low molecular-weight drugs to macromolecules was developed. The model is based upon the ultrastructure of the cornea and the sclera; all parameters correspond to the geometrical and physicochemical characteristics of the eye and solutes, and are estimated from independent literature data. Comparison of our predictions with a large set of experimental data shows good agreement. The model suggests that important factors controlling diffusion rates across the sclera and stroma are tissue hydration, tissue thickness, and the size and volume fraction of proteoglycans present in these tissues. Applications to ocular drug delivery and treatment of glaucoma are discussed.