PGD 2 is the major mediator released by mast cells during allergic responses, and it acts through two different receptors, the D prostanoid receptor 1 (DP1) and DP2, also known as CRTH2. Recently, it has been shown that PGD 2 inhibits the migration of epidermal Langerhans cells to the skin draining lymph nodes (LNs) and affects the subsequent cutaneous inflammatory reaction. However, the role of PGD 2 in the pulmonary immune response remains unclear. Here, we show that the intratracheal instillation of FITC-OVA together with PGD 2 inhibits the migration of FITC+ lung DC to draining LNs. This process is mimicked by the DP1 agonist BW245C, but not by the DP2 agonist DK-PGD 2. The ligation of DP1 inhibits the migration of FITC-OVA+ DCs only temporarily, but still inhibits the proliferation of adoptively transferred, OVA-specific, CFSE-labeled, naive T cells in draining LNs. These T cells produced lower amounts of the T cell cytokines IL-4, IL-10, and IFN-γ compared with T cells from mice that received FITC-OVA alone. Taken together, our data suggest that the activation of DP receptor by PGD 2 may represent a pathway to control airway DC migration and to limit the activation of T cells in the LNs under steady state conditions, possibly contributing to homeostasis in the lung.