pH-Sensitive semi-interpenetrating networks (IPNs) based on chitosan (Cs) and acrylamide-grafted hydroxyethylcellulose (AAm-g-HEC) were prepared in the form of microspheres (MPs) by emulsion-crosslinking technique using glutaraldehyde (GA) as a crosslinker. Diclofenac sodium (DS) drug was successfully encapsulated into IPN microspheres by varying the ratio of Cs and AAm-g-HEC, % drug loading, and amount of GA. DS encapsulation of up to 83% was obtained as measured by UV spectroscopy. MPs with average particle sizes in the range of 188-310microm were obtained. MPs were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), and Differential scanning calorimetry (DSC). Diffusion coefficients (D) of water transport through the microspheres were determined using an empirical equation. In vitro release of DS from these matrices has been investigated in pH 1.2 and 7.4 media.