Hyperoxia-induced acute lung injury (HALI) is a kind of iatrogenic pulmonary dysfunction caused by the prolonged exposure to high concentrations of oxygen, which is commonly seen in the treatment of refractory hypoxemia. Agmatine (AGM), a biogenic amine metabolite of L-arginine, induces a variety of physiological and pharmacological effects in the body. In this study, we investigated the protective effect of AGM on hyperoxia-induced lung injury and explored the underlying mechanism. A series of methods were used including flow cytometry, tunnel assay, dual-luciferase reporter assay, qRT-PCR and Western blotting. The results indicate that AGM can protect hyperoxia-induced lung injury. Further studies suggest that AGM decreased the unregulated expression of IncRNA gadd7 caused by hyperoxia and due to the presence of the competitive binding of IncRNA gadd7 and MFN1 to miR-125a, AGM indirectly decreased MFN1 protein expression to inhibit the cells apoptosis. In conclusion, AGM protects hyperoxiainduced lung injury by decreasing the expression of IncRNA gadd7 to regulate MFN1 expression. (C) 2019 Published by Elsevier Inc.