Influenza A virus (IAV) infects the epithelial cells that line the surface of the respiratory tract, thereby inducing prominent necrotizing bronchitis and variable interstitial pneumonia.The severity of IAV infection is closely related to the dysfunction of apoptosis regulation.MicroRNA has distinct expression profiles in innate immunity, inflammation, and viral infection.However, the function of microRNA in IAV infection remains unknown.In this study, the function of microRNA in the development of IAV infection was investigated to identify potential drug targets.MicroRNA-155 (miR-155) expression in the lung tissues of IAV-infected mice was found to be significantly upregulated and peaked 5 d post-IAV challenge.MiR-155 overexpression in A549 cells significantly promoted cell apoptosis by inducing S-phase cell-cycle arrest.MiR-155 overexpression also inhibited the protein expression of phosphoinositide 3-kinase catalytic subunit alpha, a direct target of miR-155 identified by bioinformatics, thereby suppressing the PI3K/Akt pathway.Moreover, repressed miR-155 effectively attenuated IAV-induced interstitial pneumonia, but failed to reduce the viral load of the lung tissue in IAV-infected mice.Therefore, regulating or inhibiting miR-155 may be of therapeutic potential in influenza pneumonia.