Sustained drug delivery to the respiratory tract is highly desirable for local treatment of chronic lung diseases. In this context, a correlation of in vitro drug release with in vivo efficacy data is essential to accelerate the application of sustained drug delivery system for inhalation into the clinical setting. In this study, budesonide was incorporated into distinct chitosan-based swellable microparticles, which were characterized, and the in vitro drug release behavior determined. The particles were then given to an allergic asthma animal model as single and successive administrations, and the therapeutic response was determined by measuring cell counts, IL-4 and IL-5 levels in bronchoalveolar lavage fluid, IL-4 and IL-5 mRNA in the lung and by histopathologic examination of lung tissues. After a single administration, the time-dependent therapeutic effect of the swellable microparticles was correlated with the in vitro release behavior, which lasted for 12 or 18 h depending on the molecular weight of the chitosan. After seven days of successive treatment, the number of eosinophils decreased further and IL-4 and IL-5 mRNA expression in the lung tissue was more greatly inhibited. Moreover, the chitosan-based swellable microparticles allowed longer administration intervals (every two days), which decreased the required dose for effectiveness by 50%. These results demonstrate that chitosan-based swellable microparticles can sustain the therapeutic effect of budesonide in the respiratory tract which in principal can be applied to other drugs for the treatment of local lung diseases.