Background/purpose: Severe infection with influenza A (H1N1)pdm09 virus is characterized by acute lung injury. The limited efficacy of anti-viral drugs indicates an urgent need for additional therapies. We have previously reported that neutralization of gamma interferon IFN-gamma) could significantly rescue the thymic atrophy induced by severe influenza A (H1N1) pdm09 infection in BALB/c mice. A deeper investigation was conducted into the influence of neutralizing IFN-gamma to the BALB/c mice weight, survival rate, and lung injury. Methods: The BALB/c mice was infected with severe influenza A (H1N1)pdm09. Monoclonal antibodies against IFN-gamma were injected into the abdominal cavities of the mice. After neutralization of IFN-gamma occurred in mice infected by severe \ influenza A (H1N1)pdm09, observing the influence of neutralizing IFN-gamma to the BALB/c mice weight, survival rate, lung injury. Result: Our results here showed that anti-IFN-gamma therapy alleviated the acute lung injury in this mouse model. Neutralization of IFN-gamma led to a significant reduction in the lung microvascular leak and the cellular infiltrate in the lung tissue, and also improved the outcome in mice mortality. Several pro-inflammatory cytokines, including interleukin (IL)-1 alpha, tumor necrosis factor (TNF)-alpha and granulocyte-colony stimulating factor (G-CSF) in the bronchoalveolar lavage fluid (BALF), and the chemokines including G-CSF, monocyte chemoattractant protein-1 (MCP-1) in serum samples were found to be significantly reduced after anti-IFN-gamma treatment. Conclusion: These results suggested that IFN-gamma plays an important role in acute lung injury induced by severe influenza A (H1N1)pdm09 infection, and monoclonal antibodies against IFN-gamma could be useful as a potential therapeutic remedy for future influenza pandemics. Copyright (C) 2019, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.