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Objectives: To identify the protective role of sodium cromoglycate in mice during influenza virus infection., Design: H5N1 virus-infected mice were treated with the mast cell stabilizer sodium cromoglycate (SCG) to investigate its therapeutic effect., Sample: The nose, trachea and lungs from mice were collected., Main Outcome Measures: Virus replication and host responses were determined by plaque assay, quantitative PCR, immunohistochemistry, and histology., Results: SCG-treated mice survived better than did PBS-treated mice after H5N1 virus infection. Mild pathological changes with fewer inflammatory cell infiltration and fewer virus antigens were observed in the nose, trachea, and lungs of SCG-treated mice on days 3 and 5 post-infection. However, no significant changes in viral load in the lungs were detected between SCG- and PBS-treated mice. Furthermore, significantly decreased expression of interleukin-6, tumor necrosis factor-a, Toll-like receptor 3, and TIR-domain-containing adapter-inducing interferon-b was detected in the lungs of SCG-treated mice, and no higher expression of interferon-c was detected., Conclusion: These results suggest that SCG has therapeutic roles in H5N1 virus-infected mice by alleviating the inflammatory response rather than inhibition of viral replication in the lungs., (© 2015 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)