Air pollution is associated with many neurodevelopmental and neurological disorders in human populations. Rodent models show similar neurotoxic effects of urban air pollution ultrafine particulate matter (UFPs < 100nm (PM0.1)), collected by different methods or from various sources. Exposure to ultrafine particulate matter (UFPs < 100nm (PM0.1)) can be adversely impacting the central nervous system (CNS) by the activation of proinflammatory pathways and reactive oxygen species associated with air pollution particulate matter. We investigated hippocampal inflammatory cytokines, neurobehavioral alteration, and neuronal morphology following exposure to diesel exhaust particles (DEPs) in mice. Male mice were DEPs exposed for 14weeks. Mice exposed to DEPs showed more disorders in spatial memory and learning and depressive-like responses than control mice. Expression of hippocampal pro-inflammatory cytokine was increased among DEPs exposure mice. The density of neurons in hippocampus CA1, CA3, and dentate gyrus (DG) regions decreased in DEPs mice. Overall, these findings show that prolonged exposure to DEPs in the world's major cities can alter neurobehavioral and impair cognition.