Macrophage play important role in acute lung injury (ALI). This study aims to explore the possible role of Shp2 in regulating macrophage 1 (M1) in ALI progression. ALI was induced in rats by intravenous injection of lipopolysacharide (LPS). Lentivirus was used to knock down Shp2 expression. Lungs from LPS-induced ALI rats were evaluated by H&E staining and wet/dry lung weight ratio (W/D ratio) measurement. The expression of inflammatory cytokines IL-1 beta, TNF-alpha and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. The expressions of M1 biomarker (iNOS) and macrophage 2 (M2) biomarker (Arg-1) in lung tissues and macrophages were measured by immunofluorescence and western blot. The ratio of M2/M1 was detected by flow cytometry. Inflammatory cytokines were highly expressed in ALI rat models, in which elevated expression of iNOS and decreased Arg-1 expression were detected. Shp2 was found to be highly expressed in lung tissues of ALI rat models. LPS treatment in NR8383 cells lead to increased M1 phenotype and elevated expression of Shp2. Suppression on Shp2 expression can counteract the LPS-induced effect and further attenuate ALI progression. Evidence collected from ALI rat and cell models showed that suppression Shp2 expression in macrophages can inhibit M1 phenotype to attenuate ALI progression.