Background: Acute lung injury (ALI) is a potentially fatal disorder that is largely caused by inflammation. Sodium isostevanol (STV-Na) is a terpenoid produced from stevioside, which possesses anti-inflammatory and antioxidative stress characteristics. nevertheless, it is still unclear how STV-Na affects ALI. Therefore, we investigated the possible STV-Na therapeutic impacts on lipopolysaccharide (LPS)-induced (ALI). Methods: We employed hematoxylin-eosin staining to observe the impact of STV-Na on lung histopathological alterations and used kits to detect the oxidative stress status of lung tissues, such as superoxide dismutase, malondialdehyde, and glutathione. The reactive oxygen species and myeloperoxidase expression in the tissues of lung was assessed by immunofluorescence and immunohistochemistry. Additionally, we detected the impact of STV-Na on inflammatory cell infiltration in lung tissue using Wright-Giemsa staining solution and immunohistochemistry, which was found to reduce inflammation in lung tissue by enzyme-linked immunosorbent assay. Finally, using WB, we examined the impact of STV-Na on the TLR4/NF-kB pathway. Results:We observed that STV-Na attenuated lung histopathological alterations in LPS-induced lung damage in mice, reduced infiltration of inflammatory cell and oxidative stress in the tissue of lung, and via the TLR4/ NF-kB pathway, there is a reduction in the inflammatory responses in mouse lung tissue.Conclusions: These outcomes indicate that the response of inflammatory cells to LPS-induced ALI in mice was attenuated by STV-Na.