This study aimed to elucidate the protective role of grape seed extract (GSE) in mitigating the oxidative stress, inflammatory and apoptotic insults on lung tissue induced by formaldehyde (FA) inhalation in rats. Fifty adult albino rats were divided into 5 groups; (1) was negative control, (2) was FA-challenged group exposed to 10 ppm FA, (3) was FA-challenged group exposed to 20 ppm FA, (4) was orally administered with GSE (150 mg/kg b. wt.) prior exposure to 10 ppm FA and (5) was orally administered with GSE (150 mg/kg b. wt.) prior exposure to 20 ppm FA. Pro-oxidants (NO, MDA and H2O2), antioxidant enzymes (GSH-Px, SOD and CAT) and apoptotic markers (Bcl- 2 and P53) were quantified in lung tissue. The inflammatory cytokines (IL-6, IL-8 and IL-10) were estimated in serum. Histological examination of lung tissue was performed. In comparison with the negative control, FAchallenged groups recorded significant increase in lung NO, H2O2, MDA and P53 as well as serum IL-6 and IL-8 levels accompanied with significant decrease in lung GSH-Px, SOD, CAT, Bcl-2 and serum IL-10 in a dose dependent manner. Histological examination of lung tissue of rats in FA-challenged groups showed peribronchiolar lymphoid hyperplasia with severe congestion in the pulmonary blood vessels. Pre-treatment with GSE elicited significant modulation in the pro-oxidants, inflammatory cytokines, antioxidant enzymes and apoptotic markers. These findings were documented by the histological examination of the lung tissue. In conclusion, the present work provided a clear evidence for the protective role of GSE against lung injury induced by FA inhalation in rats.