In this article, to discover an innovative drug release system, ciprofloxacin hydrochloride-loaded blending films of chitosan (CS)/ethyl cellulose (EC) microspheres were prepared. Two steps were adopted in the film forming process. The first was formation of the drug-loaded EC microspheres in CS solution by solvent remove/solvent evaporation methods; then, the composite films were made by casting and solvent evaporation. The results were that the drug-loaded round EC microspheres dispersed asymmetrically in the CS films and largely improved the release time. Moreover, the drug-loaded blending film containing 0.5 g EC microspheres prepared at 90 °C showed highlighted extended release property. The drug was stable in the blending films, which expressed good cytocompatibility proved by MTT test. The film should be a promising carrier for controlled and extended drug release system in pharmaceutical applications.