Aim/Background: In traditional Chinese medicine, Polygonum chinense has been used to treat influenza. However, little information is available from current studies regarding the anti-influenza pharmacological activities of P. chinense water decoction (PCWD) and its underlying mechanisms. The present study aimed at investigating the treatment of PCWD on acute lung injury (ALI) induced by the H1N1 influenza A virus (IAV) and its underlying mechanisms. Materials and Methods: Mice were infected with IAV. PCWD (300 and 600 mg/kg/day) and ribavirin (100 mg/kg/day) were orally administrated to mice. Mice survival rate was observed for 15 days after inoculation. On day 5 after virus infection, serum and lung tissues of mice were collected for the analysis of lung index, virus titers, cytokines, histopathology, and immunohistochemistry. Results: PCWD significantly lessened ALI and improved survival rate induced by H1N1. PCWD also decreased the 5th day lung index and ameliorated the injuries, inflammatory cells infiltration, and lung edema. PCWD reduced the level of tumor necrosis factor-α and interleukin-6. PCWD obviously decreased hemagglutinin titer in the lungs. Immunohistochemistry showed that PCWD obviously inhibited TLR-4 and p-NFκB p65 expression. Conclusion: PCWD can alleviate ALI induced by IAV through inhibiting inflammation.