Blend microspheres of chitosan (CS) and guar gum (GG) have been prepared using the water-in-oil (w/o) emulsion method. Cefadroxil was loaded into the microspheres and cross-linked with glutaraldehyde, leading to the formation of a semi-interpenetrating polymer network (IPN) structure. The microspheres have been characterized by scanning electron microscopy, X-ray diffraction and differential scanning calorimetry. Scanning electron micrographs showed the formation of non-uniform microspheres with the rough surface. X-ray diffraction and differential scanning calorimetry studies of the plain and the drug-loaded microspheres indicated that drug is dispersed at the molecular level in the semi-IPN matrix. In vitro dissolution experiments performed in pH 7.4 buffer medium indicated a sustained and controlled release of cefadroxil from semi-IPN microspheres up to 10 h. The amount of drug loaded into microspheres, CS-GG composition of the blend and the amount of cross-linking agent used have shown dependencies on the release of cefadroxil from the semi-IPN microspheres.