AbstractNovel pH‐dependent chitosan/poly(ethylene glycol) (PEG) membranes were developed for oral drug delivery. The preparation of these membranes involved a solution‐mediating process with glucose addition at different pHs. Fourier transform infrared/attenuated total reflectance showed that the Schiff‐base reaction was favored at high pHs and high glucose concentrations. X‐ray diffraction analysis showed a continuous increase in the glucose addition transformed the chitosan/PEG samples into amorphous polymers. The equilibrium swelling measurements showed that the swelling ratio of the solution‐mediated membranes decreased as the glucose concentration increased, and this was demonstrated by degree‐of‐mediation analysis. The glucose‐mediated membranes had different degrees of mediation, which depended on the pH and glucose concentration. The in vitro release profiles of theophylline‐loaded, pH 6 treated, glucose‐mediated membranes showed that the theophylline release decreased as the glucose concentration increased. Also, the release behavior of the theophylline from the glucose‐mediated membranes varied with the pH of the release medium, the glucose concentration, and the final pH of the glucose‐mediated chitosan/PEG gels. Chitosan/PEG membranes prepared by a basic glucose‐mediated process could lead to successful applications in localized drug delivery to the intestine. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1083–1094, 2005