The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Since dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating of DC subsets on airway inflammation by acute CS exposure. CS-exposed mice (5 days) were treated with Flt3L (fms-like tyrosine kinase 3 ligand) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. Flt3L treatment decreased the number of inflammatory cells in the BALF of the smoke-exposed mice and increased these in lung tissue. DC modulation reduced IL-17 and increased IL-10 levels, which may be responsible for the suppression of the BALF cells. Furthermore, depletion of pDCs led to increased infiltration of alveolar macrophages while restricting the presence of CD103⁺ DCs. This study suggests that DC subsets may differentially and compartment-dependent influence the inflammation induced by CS. pDC may play a role in preventing the pathogenesis of cigarette smoke by inhibiting the alveolar macrophage migration to lung and increasing CD103⁺ DCs at inflammatory sites to avoid extensive lung tissue damage.