Acute Lung injury (ALI) is one of the most common organ dysfunctions in critically ill patients and is associated with lung inflammation and apoptosis. However, the cellular interactions in the lung contributing to its pathophysiology are unclear. The objective of this study was to determine the contribution of dendritic cells (DCs) to lung apoptosis, inflammation and neutrophil recruitment during ALI resultant from hemorrhagic shock (Hem)/sepsis (CLP).Using a dual insult model of Hem followed 24h later by CLP, we measured, 24h after CLP, caspase 3 activity, lung myeloperoxidase (MPO) and pro‐inflammatory cytokine production in the lung and plasma of CD11c‐Diphteria Toxin (DT) Receptor conjugated vs background mice injected intraperitoneally (IP) or intratracheally (IT) with DT prior to shock.Systemic DC depletion (IP DT) was associated with a marked increase in IL‐6, TNF‐α and MCP‐1 concentrations after Hem/CLP, whereas lung apoptosis and neutrophil recruitment (MPO) were not modified in comparison with background mice. Similar results were observed after local lung DCs depletion (IT DT). Preliminary experiments suggest that this DC effect is mediated through the recruitment and/or activation of macrophage to/in the lung. Thus the resident and possibly recruited DCs may play here‐to‐for unappreciated role in suppressing lung inflammation and promoting the resolution of ALI. (NIH‐HL73525)