Abstract： Objective To study the activation of macrophage and upregulation of CD40 in neutropenic and nonneutropenic lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Forty mice were randomly divided into four groups (neutropenic septic group,neutropenic control group,non neutropenic septic group and normal control group).The pathologic changes of mice lungs were observed after hematoxylin and eosin staining.CD40 expression was determined by flow cytometry.Cytokine tumor necrosis factor-α levels from bronchoalveolar lavage fluid (BALF) and serum were measured by ELISA.Results The average weight and peripheral blood white cell counts were increased significantly in the neutropenic group as compared to the non neutropenic group before the rats were sacrificed [(181.13 ± 16.94) g vs (168.56 ±5.03) g,(9.54 ± 1.25) × 109/L vs (2.56 ± 1.12) × 109/L,P ＜0.05,respectively].The cell counts in BALF were higher in neutropenic septic and non neutropenic septic groups compared to the normal control group [(3.33 ±0.26) × 106/L,(3.23 ± 0.06) × 106/L,(1.68 ± 0.23) × 106/L,P ＜ 0.05].The concentration of tumor necrosis factor-α from serum were increased significantly in neutropenic septic and non neutropenic septic groups as compared to the normal control group [(2 337.08 ± 1 148.85) pg/ml,(2 274.01 ± 1 569.37) pg/ml,(96.20 ± 93.69) pg/ml,P ＜ 0.05].The CD40 molecular expressions were higher in neutropenic septic and non neutropenic septic groups compared to the normal control group [(42.06 ± 11.90) ％,(46.38 ±7.42) ％,(21.62 ± 4.86) ％,P ＜ 0.01].Conclusion Upregulation of CD40 molecule induces the inflammatory cytokines releasing,then leads to ALI.Therefore both the inflammatory cytokines and CD40 play vital role in the pathogenesis of ALI.