The main aim of this study was to compare two microspheres, chitosan (CTS) and CTS/β-cyclodextrin (β-CD), made by spray-drying, as pulmonary sustained drug-delivery carriers. Theophylline (TH) was used as a model drug. The characteristics of the microspheres and in vitro release were studied. The yield of CTS/β-CD microspheres was 46.1%, which was higher than that of the CTS microspheres (36.5%). The drug loads of the CTS and CTS/β-CD microspheres were 22.7 and 21.1%, respectively, whereas the encapsulation efficiencies were 90.7 and 91.4%, respectively. The distribution of 50% [(diameter) d (0.5)] of the CTS microspheres was below 6.49 mm and that of the CTS/β-CD microspheres was below 4.90 mm. Scanning electron microscopy showed that both microspheres yielded a spherical shape with smooth or wrinkled surfaces. Fourier transform infrared spectroscopy demonstrated that the carbonyl group of TH formed hydrogen bonds with the amide group of CTS and the hydroxyl group of b-CD. The swelling ability of the two microspheres was more than three times their weight, and their humidity rates attained equilibrium within 24 h. The ciliary beat movement times of CTS and CTS/β-CD microspheres were 493.00 and 512.33 min, respectively, which indicated that the two microspheres effectively reduced the ciliotoxicity and possessed better adaptability. In vitro release of TH from CTS/β-CD microspheres was slower than that from CTS microspheres at pH 6.8 and provided a sustained release of 72.0% within 12 h. The results suggest that CTS/β-CD microspheres are a promising carrier for sustained release for pulmonary delivery. 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 1183-1190, 2007