Several studies have demonstrated that the pulmonary delivery of small nucleic acids could be used in the management of various lung diseases and infections. Most formulations used in those studies are liquid aerosol which are not desirable for macromolecules like nucleic acids and proteins that are prone to hydrolysis and enzymatic degradation. A stable solid formulation of nucleic acid for inhalation is in demand. This study focused on formulating small nucleic acids (herring sperm DNA, with size below 50 base pairs) into inhalable dry powders by spray drying using mannitol and L-leucine as the excipients. Formulations of different compositions were prepared and their in vitro aerodynamic performances were evaluated using the Next Generation Impactor. The addition of L-leucine, as a dispersion enhancer, increased the fine particle fraction (FPF) by about 50% compared to those without L-leucine. At 0.75% w/w of DNA, powders with excipients of mannitol: L-leucine at 8:2 or 5:5 achieved a FPF of 62%. When the amount of DNA was increased to 2% w/w, formulation with mannitol: L-leucine equalled 8:2 gave the highest FPF at 58%.