To date, although a promising anti-inflammatory activity of oligomeric proanthocyanidins (OPCs) has been observed in asthma, the mechanism responsible for these immunomodulatory properties remains obscure. Dendritic cells (DCs) that reside in the airway have been widely perceived as an important contributor to asthma. Our study was to demonstrate OPCs' effects on maturation and immunoregulation of pulmonary CD11c+ dendritic cells (DCs). BALB/c mice were exposed to ovalbumin (OVA) to induce murine model of asthma. In addition, pulmonary DCs and bone marrow-derived DCs (BMDCs) cultures were used to evaluate impacts of OPCs on DCs function. The results obtained here indicated that OPCs treatment dramatically reduced airway inflammation, such as the infiltration of inflammatory cells and the levels of allergen-specific serum IgE and Th2 cytokines. The expression of co-stimulatory molecules especially CD86 distributed on pulmonary DCs and bone marrow-derived DCs (BMDCs) also markedly declined. The phosphorylation of cAMP responsive element-binding protein (CREB) was significantly inhibited while no changes were observed in the expression of cAMP responsive element modulator (CREM). By transferring BMDCs into the airways of naïve mice, we found that OPCs-treated DCs (DC + OVA + OPC) were much less potent in promoting CD4+ T cells proliferation than OVA-pulsed DCs (DC + OVA), followed by the ameliorated eosinophilic inflammation in airway. Our findings tailor a novel profile of OPCs in the regulation of DCs function, shedding new light on the therapeutic potential of OPCs in asthma management.