Objective To investigate the effect and mechanisms of ficolin (Fcn) in acute lung injury induced by lipopolysaccharide (LPS) stimulation. Methods SPF C57BL/6 mice and ficolin gene knockout mice were randomly divided into 6 groups：WT-PBS group， WT-LPS group， Fcna^－/－-PBS group， Fcna^－/－-LPS group， Fcnb^－/－-PBS group and Fcnb^－/－-LPS group, according to the experimental requirements. Acute lung injury model was established after intranasal inoculation with 5 mg/kg LPS for 2 days. H&E staining was used to detect pathological damage of lung tissue. Flow cytometry was used to detect the proportions of neutrophils and macrophages in lung tissue. Western blotting was used to detect the expression of inducible nitric oxide synthase (iNOS) in lung tissue. Bone marrow derived macrophages in wild-type and ficolin knockout mice were isolated and cultured in vitro. After LPS stimulation, the expression of iNOS in cells and the concentration of nitric oxide (NO) in supernatant were detected. Results A mouse model of acute lung injury induced by intranasal inoculation of LPS was successfully established. LPS stimulation aggravated lung pathological injury, with increased pulmonary alveolar fusion and many inflammatory cells infiltration. Besides, the proportions of neutrophils and interstitial macrophages were significantly increased. The expression of iNOS and the production of NO in mouse lung tissue and bone marrow derived macrophages were significantly increased after LPS stimulation in vivo and in vitro. However, knockout of ficolin significantly reduced the recruitment of interstitial macrophages after LPS stimulation. Furthermore, knockout of ficolin ameliorated LPS induced acute lung injury, with reduced iNOS expression and NO production. Conclusion Ficolin can aggravate LPS induced acute lung injury by promoting polarization of M1 macrophages, which may be a potential therapeutic target for acute lung injury.