The objective of this study is to clearly assess the surface energy effect of co-spray-dried mannitol (co-SDM) particles with polyethylene glycol (PEG) on the aerosolization performance in a dry powder inhalation (DPI) formulation. From the results of in vitro deposition studies in the model DPI formulation containing salbutamol sulphate (SS), the effect of PEG molecular weight (MW) and formulated amount of PEG in the co-SDM on the aerosolization performance was evaluated. The fine particle fraction (FPF) of SS in the formulation containing co-SDM with PEG 20000 was superior to that in the formulation containing spray-dried mannitol (SDM) without PEG. On the other hand, the FPFs of SS were found to be influenced by the PEG ratio and MW of PEG used in the formulation of co-SDM with PEG. The surface energies of co-SDMs with PEG were measured by an IGC technique. It was considered that the lower dispersive component of the surface energy of co-SDM may contribute to a higher FPF of SS when using PEG with a high MW. Moreover, the elevation of the basic (electron donor) energy might result in the decrease of FPF of SS when using PEG with low MWs. The elevation of the basic (electron donor) energy of a co-SDM would relate to both/either the difference in the adhesion force to the SS and/or the difference in the hygroscopicity of each PEG.