Rationale: Strategically located beneath the alveolar epithelial barrier, dendritic cells of the lung are centrally involved in the sampling and processing of inhaled antigens. However, the contribution of dendritic cells to acute lung inflammation induced by inhaled bacterial toxins is largely unknown. Objectives: To determine the effect of increased lung dendritic cell numbers elicited by Fms-like tyrosine 3-kinase ligand on the acute lung inflammatory response to Escherichia coli lipopolysaccharide and Klebsiella pneumoniae infection. Methods: Mice were pretreated with Fms-like Tyrosin 3-Kinase Ligand either in the absence or presence of anti-CD11a antibodies to block the Flt3L-elicited lung DC accumulation or were made transiently neutropenic and then challenged with Escherichia coli lipopolysaccharide or Klebsiella pneumoniae. Results: Fms-like Tyrosin 3-Kinase Ligand-pretreated mice challenged with lipopolysaccharide responded with drastically increased numbers of both lung parenchymal and alveolar dendritic cells along with an aggravated neutrophilic alveolitis, elevated TNF and IL-12 levels, and a strongly increased lung permeability compared to LPS or Flt3L only treated mice. Anti-CD11a mediated blockade of lung dendritic cell accumulation significantly attenuated the lung permeability developing in response to LPS, whereas transient neutropenia did not affect lung permeability changes. Finally, Fms-like Tyrosin 3-Kinase Ligand pre-treated mice responded with increased lung permeability and decreased survival upon infection with K. pneumoniae. Conclusion: Lung dendritic cells actively participate in the early inflammatory response to both inhaled bacterial toxins and live bacteria and play a yet unrecognized role in regulating lung barrier integrity.