The neuropeptide vasoactive intestinal peptide (VIP), released within lymphoid organs from nerve terminals and/or immune cells, plays a significant anti-inflammatory role. It was reported that VIP can induce regulatory dendritic cells (DCs) and promote Th2-type responses. However, the regulatory effect of VIP on the migration and expression of chemokine receptors by DC is mostly unknown. In the present study, we show that VIP exerts a differential effect on the expression of CCR1 and CCR7 by lipopolysaccharide (LPS)-treated mature DCs (mDCs) at both protein and mRNA levels. It up-regulates CCR1 expression but down-regulates CCR7 expression in LPS-stimulated mature DC, thereby differentially regulating the migration of mature DCs in response to CCL5 and CCL19. Our data indicate that VIP functions as a key endogenous anti-inflammatory agent by inhibiting migration of mDCs to draining lymph nodes, thus preventing the induction of an inflammatory immune response.