Quercetin (Qu) is an important polyphenolic flavonoid which exhibits tremendous antioxidant, anti-inflammatory and other health promoting effects. The aim of the current study was to explore the therapeutic role of Qu on benzo(a)pyrene [B(a)P]-induced lung injury in rats. B(a)P was given to the rats at dose of 50 mg/kg b.w. for continues 8 weeks through oral gavage. The rats were treated with Qu at dose of 50 mg/kg b.w prior 30 min before the oral administration of B(a)P. The effects of Qu were studied by measuring the level of lactate dehydrogenase (LDH), anti-oxidant enzymes, lipid peroxidation, inflammatory cytokines, lung tissues architecture and expression of cyclooxygenase-2 (COX-2). The level of pro-inflammatory cytokines such as IL-1β (27.30 vs. 22.80 pg/mL), IL-6 (90.64 vs. 55.49 pg/mL) and TNF-α (56.64 vs. 40.49 pg/mL) increased significantly and antioxidant enzymes decreased significantly in benzopyrene-induced lung injury in comparison to the control group. The treatment with Qu potentially reversed the effects of B(a)P to a great extent, as it led to the enhancement of antioxidant enzymes and decreased proinflammatory cytokines level. A significant surge of VEGF level was noticed in the B(a)P group as compared to the control group, while the Qu treatment groups exhibited less angiogenesis as lower level of VEGF levels, compared with the B(a)P treatment group. The Qu treatment significantly decreased the degrees of histopathological changes and collagen deposition in B(a)P-induced lung injury. The B(a)P-treated group showed higher cytoplasmic expression of COX-2 protein, which significantly decreased in the Qu treatment group. These outcomes recommend an effective role of Qu in the protection of lung injury against B(a)P through the regulation of the inflammatory factors, oxidative stress and the maintenance lung tissue architecture.