Ambient particulate matter (PM) is associated with adverse health consequences. However, the influence of PM on the innate immune system is poorly understood. The aim of the present study was to examine the effect of diesel particulate matter 2.5 μm (PM 2.5 , SRM1650b) on dendritic cells. PM 2.5 significantly reduced cytokine levels of interleukin (IL)-12 p40, IL-6 and TNF-α levels in CpG-DNA (TLR9 ligand)-stimulated dendritic cells. To determine the mechanisms underlying this observed inhibition induced by PM 2.5 , western blot analysis was conducted. PM 2.5 was found to downregulate ERK1/2, JNK1/2, p38 MAPKs, and NF-κB pathways. PM 2.5 exposure decreased TLR9-dependent NF-κB and activator protein (AP-1) reporter luciferase activities. Our findings demonstrate that PM 2.5 reduced the production of cytokines which may be associated with inhibition of MAPK and NF-κB signaling pathway. Further, data suggest the immunosuppressive effect of PM 2.5 on the innate immune cells may lead to serious damage to the host immune system.