Quercetin alleviates PM2.5-induced chronic lung injury in mice by targeting ferroptosis. This study investigates the role of ferroptosis in PM2.5-induced lung injury and the protective effects of quercetin. PM2.5 exposure in mice caused lung inflammation, fibrosis, lipid peroxidation, and increased iron levels, which were significantly reversed by quercetin. Quercetin upregulated nuclear Nrf2 and downregulated Keap1, reducing lipid peroxidation, iron content, and ferroptosis markers. In vitro experiments showed that quercetin and dimethyl fumarate reduced lipid peroxidation and ferroptosis by activating the Nrf2-Keap1 pathway. Quercetin also decreased inflammatory cytokines and TGF-β1 in PM2.5-exposed cells. The study concludes that Nrf2 is involved in PM2.5-induced lung injury, and quercetin alleviates these effects by activating the Nrf2-Keap1 pathway. The findings suggest that quercetin may be a novel therapeutic approach for PM2.5-induced lung injury.Quercetin alleviates PM2.5-induced chronic lung injury in mice by targeting ferroptosis. This study investigates the role of ferroptosis in PM2.5-induced lung injury and the protective effects of quercetin. PM2.5 exposure in mice caused lung inflammation, fibrosis, lipid peroxidation, and increased iron levels, which were significantly reversed by quercetin. Quercetin upregulated nuclear Nrf2 and downregulated Keap1, reducing lipid peroxidation, iron content, and ferroptosis markers. In vitro experiments showed that quercetin and dimethyl fumarate reduced lipid peroxidation and ferroptosis by activating the Nrf2-Keap1 pathway. Quercetin also decreased inflammatory cytokines and TGF-β1 in PM2.5-exposed cells. The study concludes that Nrf2 is involved in PM2.5-induced lung injury, and quercetin alleviates these effects by activating the Nrf2-Keap1 pathway. The findings suggest that quercetin may be a novel therapeutic approach for PM2.5-induced lung injury.