A two-phase model has been proposed for a macroreticular resin catalyst to analyze the reaction activities in terms of the micro- and macroeffectiveness factors and the fraction of active sites on the surface layer. The accessibility of sulfonic acid groups was investigated through the sucrose inversion and benzene alkylation. Internal functional groups were found to be more active than external ones in the synthesis of methyl tert-butyl ether and the hydration of isobutylene. It was also shown that the distribution and local concentration level of sulfonic acid groups within a gellular microparticle of the macroreticular resin had a significant influence on the catalytic activity of 1-butene isomerization and the deactivating patterns of ethanol dehydration.