Objectives: This study focuses on the development of an inhaled dry powder (DPI) formulation of simvastatin (SV), a common anti-cholesterol prodrug, which could potentially be used for its anti-inflammatory effects and its ability to reduce mucus production as therapy for respiratory diseases. Methods: Micronized SV samples were prepared by dry jet-milling. The long-term chemical stability and physico-chemical properties of the formulations were characterised in terms of particles size, morphology, thermal and moisture responses. Furthermore, in vitro aerosol depositions were performed. The formulation was evaluated for cell viability and its effect on cilia beat activity, using ciliated nasal epithelial cells in vitro. The formulation transport across an established air interface Calu-3 bronchial epithelial cells and its ability to reduce mucus secretion was also investigated. Results: The particle size of the SV formulation and its aerosol performance were appropriate for inhalation therapy. Moreover, the formulation was found to be non-toxic to pulmonary epithelia cells and cilia beat activity up to a concentration of 10-6 M. Transport studies revealed that SV has the ability to penetrate into airway epithelial cells and is converted into its active SVA metabolite. Single dose of SV DPI also decreased mucus production after 4 days of dosing. Conclusion: This therapy could potentially be used for the local treatment of diseases like chronic obstructive pulmonary disease or cystic fibrosis, where hyper mucus production and inflammation is present.