Petroleum products—petrol, kerosene, and diesel—composed of volatile organic constituents contribute to air pollution. Exposure of gas station attendants (GSAs) to petroleum products fumes (PPFs) may account for occupation‐related predisposition to respiratory toxicity and disease pathogenesis. We simulated GSA exposure to PPF inhalation and examined their effect on oxido‐inflammatory responses, toxicity, and histopathological alterations in rat lungs, following 8‐hours daily exposure for 60 and 90 days. Reactive oxygen and nitrogen species (RONS), oxidative stress and inflammatory biomarkers, namely: superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione‐S‐transferase (GST), TNF‐α, IL‐1β, xanthine oxidase (XO), nitric oxide (NO) activity were evaluated. Besides, histopathological examination of the lungs and trachea of exposed rats, PPF exposure resulted in significant (P <.05) increases in RONS, biomarkers of oxidative stress, pro‐inflammation cytokines, and reduced (P <.05) GSH levels in rats, secondary to histopathological alteration in lungs and trachea cytoarchitecture examined in an exposure‐duration‐dependent manner. We conclude, therefore, that the observed biochemical and histological changes create a microenvironment that is permissive to diseases pathogenesis of the respiratory system via oxido‐inflammatory mechanistic pathways. [ABSTRACT FROM AUTHOR]