Antibiotic drug releasing from chitosan and acylchitosan microspheres was studied. The acylchitosan microspheres were prepared by modifying the microencapsulation process from spray-drying to spray in-liquid coagulating process for the improvement of chem-physical properties of polymer in controlling the release of antibiotic drug. A higher yield of microspheres was recovered by this improved process. Crystallinity, swelling ability, and the morphology of various microspheres were investigated by X-ray, water adsorption, and scanning electron microscopy studies. Results show that by modifying the microencapsulation process from spray-drying to spray in-liquid coagulating process, the chemical properties of the microsphere were varied from a hydrophilic chitosan microsphere to a hydrophobic acylchitosan microsphere, while the physical structure of the microsphere was varied from a porous chitosan microsphere to a dense acylchitosan microsphere. For the reasons, drug release rate of acylchitosan microspheres prepared by thf novel spray microencapsulation method were apparently depressed, and the long-acting release of antibiotic drug was possible to be achieved. (C) 19991999 John Wiley & Sons, Inc.