A multiphysics model concerning the diffusion and enzyme reaction simultaneously is developed. termed the multi-effect-coupling glucose-stimulus (MECglu) model, for simulation of the influence of ionic strength of surrounding solution on swelling behavior of glucose-sensitive hydrogel. In the system. the glucose diffusing into the hydrogel is catalyzed into the gluconic acid by the immobilized glucose oxidase and catalase to decrease pH within the gel and make the hydrogel deswell. The model consists of the Nernst-Planck diffusion-reaction equations for mobile species, Poisson equation for electric potential, and the mechanical equation for the gel displacement. Based on the theory of chemo-electro-mechanical coupled fields, the change in the ambient solution pH controls the distribution of the charge groups fixed onto the corsslinked polymeric network chains. The MECglu model is validated by comparison of equilibrium swelling between the simulations and published experimental data. For applications of design and optimization of insulin delivery system based on the glucose-sensitive hydrogels with the immobilized glucose oxidase and catalase, the sensitivity of the hydrogel is investigated within the range of practical physiological glucose concentration and ionic strength. Effect of the ionic strength is studied on mechanical and physiochemical characteristics of the hydrogel. (C) 2009 Elsevier B.V. All rights reserved.