Purpose: More than 8 million early deaths/year are attributable to air pollution, which is the main environmental cause of death worldwide. Current health concerns are especially focused on air pollution-derived particulate matter (PM), and mostly fine particles (i.e., aerodynamic diameters ≤ 2.5 µm, PM2.5), because of their ability to migrate deeply in the lungs. Despite oxidative stress-induced airway inflammation is one of the main adverse outcome pathways of PM2.5, the persistence of this underlying mechanisms, even after the exposure stops, remains poorly studied. Here, we sought also to better evaluate the oxidative and inflammatory responses in the lungs of mice exposed to urban PM2.5, 24 h after their acute exposure, and 24 h and 2 months after their subchronic exposure. Methods: Chloromethyl derivative of 2',7'-dichlorodihydrofluorescein diacetate, dithiothreitol, ascorbic acid, and glutathione assays provided the intrinsic oxidative potential of PM2.5. A/J mice (male, specific and opportunistic pathogen free, 10 weeks, n = 6/group) were exposed either for 24 h by one intranasal instillation, or for 28 days by 3 intranasal instillations/week, to 0, 10, 50 and/or 100 µg of urban PM2.5 suspended in 30 µl of sterile saline. Mice were sacrificed either 24 h after their acute exposure, or 24 h or 2 months after their subchronic exposure, and lungs were collected. Oxidative stress and inflammation were studied by nuclear factor erythroid 2-related factor 2 (NRF2) and nuclear factor-kappa B (NFB) signaling pathway activation, antioxidant enzyme activities (i.e., superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase), glutathione status, oxidative damage (i.e., 8-hydroxy-2’-deoxyguanosine, carbonylated protein, 8-isoprostane, and 4-hydroxynonenal), and cytokine secretion (i.e., tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) by TransAM, RT-qPCR, and ELISA/Luminex. Non-parametric Mann-Whitney U-test was used to look at statistical differences versus controls (p < 0.05). Results: All the tests we used revealed the high intrinsic oxidative potential of the PM2.5. Dose-dependent activation of NRF2 and NFB signaling pathways, enzymatic and non-enzymatic antioxidant defense alterations, DNA and protein oxidative damage, and cytokine secretion were reported in mice acutely exposed (p < 0.05). All these features were reinforced and others appeared (i.e., lipid peroxidation) 24 h after the subchronic exposure (p < 0.05). Most of them persisted, at a lesser extent, 2 months after exposure cessation (p < 0.05). Taken together, these results confirmed that any exposure to PM2.5 induced significant oxidative and inflammatory responses within the lungs. Longer the exposure duration was, highest the harmful lung effects were. Interestingly, their persistence despite exposure cessation supported a high retention and slow elimination of these particles, which can also continue to exert their toxicity in the lungs.