A three-dimensional pore network model has been developed to simulate anisotropic multicomponent diffusion and reaction in polycrystalline microporous media with coexisting intracrystalline micropores and intercrystalline mesopores (i.e., defects). Transport in these pores is modeled with the generalized Maxwell-Stefan surface diffusion model proposed by Krishna [11] and the Knudsen diffusion model, respectively. A new feature highlight of this model is the representation of polycrystalline media with a crystallite-pore network model. In contrast to previous pore network models, the crystallite-pore network model has the novel aspect of modeling the anisotropic transport inside the crystallites forming a polycrystalline layer by assigning to every crystallite two parameters to describe its orientation. The model was applied to simulate xylene isomerization in a polycrystalline ZSM-5 zeolite membrane, which had been experimentally investigated in a Wicke-Kallenbach cell by Haag et al. [13]. First, their experimental data were used to estimate adsorption and diffusion parameters of the xylene isomers in the ZSM-5 membrane via fitting single-gas permeance data of the xylene isomers. Second, adopting these parameters, the experimental data for xylene isomerization were used to determine kinetic parameters for xylene isomerization in the ZSM-5 membrane. Finally, effects of selected structural parameters - concentration of defects, connectivity of defects, crystallite orientation, and crystallite size - were investigated using the obtained adsorption, diffusion, and reaction parameters. The simulation results show that high selectivity towards p-xylene requires a low concentration of defects in the polycrystalline layer and a low loading of xylene isomers in the membrane. The novel crystallite-pore network model is also applicable to many other reaction systems.