Immobilized glucose isomerase is used widely for converting glucose to fructose by enzymatic isomerization. The process takes place in a packed-bed reactor consisting of microporous particles with distributed pore sizes and interconnectivities. The efficiency of the process is, however, significantly affected by deactivation of the microporous particles. Although various mechanisms of the deactivation process have been proposed in the past, the role of the morphology of the particles and the packed bed has not been studied, as all the previous attempts for modelling this phenomenon have used a continuum formulation of the problem based on the classical equations of mass transport and reaction, without any regard for the effect of the pore space morphology. In this paper, we study deactivation of the microporous particles as a percolation process by developing a network model of the pore space with distributed pore sizes and interconnectivities. The network model is used to study several possible mechanisms of deactivation of the particles, and to identify the most plausible one.