Li, Be, Al, Cr, Co, Ni, Se, Cd, Ba, Ti and Pb were deposited in rat PFC after PM2.5 exposure. Neurotransmitters were significantly altered in PFC of CA rats. The NLRP3 signalling pathway was more activated in Nrf2−/− than WT mice after PM2.5 exposure × 9 wk. The Nrf2/NLRP3 signalling pathway, by modulating inflammation, might play an important role in ambient PM2.5-induced depression. This evidence concerns the gene NFE2L2 and depressive disorder.