Abstract: Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson’s disease (PD). We exposed mice to coarse particles (PM10: 2.5–10 µm) for short (5 days) and long (8 weeks) durations via intratracheal instillation. Long-term PM10 exposure exacerbated motor impairment and dopaminergic neuron death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Short-term PM10 exposure resulted in both pulmonary and systemic inflammatory responses in mice. We further investigated the mechanism underlying PM10- induced neurotoxicity in cocultures of lung LA-4 epithelial cells and RAW264.7 macrophages. PM10 treatment elicited a dramatic increase in proinflammatory mediators in LA-4/RAW264.7 coculture. Treating BV2 microglial cells with PM10-treated conditioned medium induced microglial activation. Furthermore, 1-methyl-4-phenylpyridinium (MPP+ ) treatment caused notable cell death in N2A neurons cocultured with activated BV2 cells in PM10-conditioned medium. Altogether, our results demonstrated that PM10 plays a role in the neurodegeneration associated with PD. Thus, the impact of PM10 on neurodegeneration could be related to detrimental air pollution-induced systemic effects on the brain.