Background: The present investigation is designed to evaluate the antioxidant and protective efficacy of the brown alga, Hydroclathrus clathratus (C.Agardh) M. Howe, against copper-induced lung injury in male albino rats. The present study was carried out on 24 adult male albino rats, they were randomly divided into four groups (n = 6) (A group, control rats; B group, rats received 100 mg/kg body weight of H. clathratus ethanolic extract; C group, rats augmented with 100 mg/kg body weight of CuSO 4 ; and D group, rats were supplemented with 100 mg/kg of CuSO 4 and 100 mg/ kg of H. clathratus ethanolic extract). All the experimental treatments were given orally and daily for 28 days. Results: It was showing that Cu treatment was found to induce lung toxicity, histopathologically, Cu revealed severe degenerative and necrotic lesions in the lung. Also, Cu caused a significant decrease in glutathione-S-transferase (GST) count and glutathione (GSH); meanwhile, malondialdehyde (MDA) content was increased. Consistently, mRNA and protein expression levels of proapoptotic (caspase-3 and Bax) marker showed a significant upregulation, whereas the anti-apoptotic (Bcl-2) level was significantly downregulated in lung tissues of CuSO 4-intubated groups. Moreover, H. clathratus plus CuSO 4-treated group showed improvement in the histopathological changes of lung injury. The bronchi and bronchioles appeared like those of the control, where the alveoli showed thin septa in some parts and thickened septa in other parts. Conclusion: Findings revealed that the natural antioxidant activity of H. clathratus could protect the lung tissue from the damage produced by CuSO 4 .