Diesel exhaust (DE) is a major contributor to air pollution globally. Fine and ultrafine particulate matter make up a large portion of its components. For some time, exposure to high levels of traffic related particulate air pollution has been associated with adverse health effects of the respiratory system and the cardiovascular system. More recently, epidemiological studies have shown that high level exposures are also associated with endpoints in the central nervous system. Specifically, exposure may be associated with increased incidence of dementia, Alzheimer’s disease (AD), and to a lesser extent, Parkinson’s disease (PD), as well as distinctive neuropathology associated with these conditions. Posthumous examination of the brains of individuals who suffer from neurodegeneration have shown an increase in levels of oxidative stress and indices of neuroinflammation, such as increased levels of TNF-α and IL-6. Moreover, while the brains of even healthy elderly people tend to exhibit a more reactive glial phenotype, sufferers of neurodegeneration show evidence of a higher degree of microglial activation compared to their nondiseased counterparts. Significantly, experimental exposures of animals to DE have determined that acute exposures can significantly increase biomarkers of oxidative stress, microglial activation, and neuroinflammation. High level chronic exposures of animals to DE, which may be considered analogous to high level occupational exposures, have also been shown to increase levels of markers of neurodegeneration such as Tau-pS199, Aβ42, and α-synuclein, indices which are significantly increased in individuals with AD and PD. Conditions of oxidative stress and neuroinflammation, and the intrinsically connected signaling activity of microglia are also factors that affect adult neurogenesis, the birth of new neurons in the postnatal brain. Regulation of adult neurogenesis appears to be strongly connected to cognitive function, as many animal experiments where adult neurogenesis is perturbed show a lack of cognitive function in the domains corresponding to the affected brain regions. This may be due to the preferential involvement of young neurons in the process of long term potentiation, which is a factor in synaptic plasticity, or the strengthening and weakening of connections between neurons over time, a process important to memory. Due to the presence of perturbations of neurogenesis in the brains of individuals suffering from AD in particular, and the absence of cognitive deficits in individuals with AD-type pathology and conserved neurogenesis, the preservation of adult neurogenesis may be an important point of intervention in the prevention of cognitive decline in the elderly. In this work, we addressed whether exposure to DE suppresses adult neurogenesis, and if so, whether or not male animals would show an increased susceptibility to the neurotoxicity of DE relative to females. Due to the importance of microglial signaling activity in the regulation of adult neurogenesis, we also wanted to see whether attenuation of microglial activation and neuroinflammation through pharmacological intervention could potentially mitigate this effect. We also examined whether or not a subchronic exposure to DE of either 3 weeks or 10 weeks would be sufficient to cause increases in levels of markers of neurodegeneration in the regions examined. In response to acute DE exposure, we found that male animals showed reduced proliferation in all regions examined. Similarly, adult neurogenesis, as assessed by survival of adult born neurons, was also impaired in all regions investigated. These effects were mitigated by blocking microglial activation through pretreatment with the PPARγ agonist pioglitazone. By contrast, adult neurogenesis only reduced in females in the olfactory bulb. We also determined that a three-week exposure was only sufficient to significantly increase α-synuclein in midbrain, but that a ten-week exposure was able to increase levels of Dyrk1a, Aβ42, and Tau-pS199. This work supports the idea that exposure to high levels of traffic-related particulate air pollution, as modeled by DE exposure, may significantly contribute to the development of neurodegenerative conditions through a mechanism likely to involve neuroinflammation and microglial activation, and could contribute to cognitive decline through dysregulation of adult neurogenesis.