Background: Simvastatin (SV) is an inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, used for lowering cholesterol levels in myocardial infarction prevention. Recently, there has been increasing evidence that SV possess anti-inflammatory properties and that these could be useful in decreasing the inflammation processes in pulmonary disease. Hence, this study focuses on the development of SV dry powder inhalation (DPI) formulation, as a novel therapy for inflammation and mucus over production in chronic respiratory diseases. Methods: Micronized SV powders were prepared by dry jet milling and physico-chemical properties of the formulations were characterised in terms of particles size. Also, the in vitro aerosol deposition of the formulation was studied. In addition, SV was evaluated for its effects on cilia beat frequency using primary nasal epithelial cells. Furthermore, the formulation was assessed for its muco-inhibitory effect on an established air interface Calu-3 cell model. Results: SV particle size of the formulation was suitable for inhalation therapy, with a fine particle fraction (FPF, defined as percentage of SV mass deposited from stage three to filter, as a function of the ex-valve dose (ED), corresponding to the cut-off size ≤ 5 μm) of 44.62 ± 5.77 %. Additionally, the SV was found to be non-toxic on the nasal cilia up to a concentration of 10-6M, and to decrease mucus production in Calu-3 after 4 days exposure to a single dose of SV DPI. Conclusion: This therapy could potentially be used for the local treatment of respiratory diseases, where hyper mucus production and inflammation is present.