OBJECTIVE Bone marrow-derived mesenchymal stem cells (MSCs) can serve as a vehicle for gene therapy. FGF2 (basic fibroblast growth factor) is a multifunctional growth factor and exhibits diverse function in different cell types, it also has pleiotropic effects in different tissues and organs, including potent angiogenic effects and an important role in the differentiation and function of the central nervous system. We hypothesized that MSC-based FGF2 gene therapy might be a potential therapeutic approach for lipopolysaccharide (LPS)-induced lung injury. MATERIALS AND METHODS MSCs were isolated from 6 week-old inbred male mice and transduced with the FGF2 gene, using a lentivirus vector. RESULTS In the in vivo mouse model, the LPS-induced lung injury was markedly alleviated in the group treated with MSCs carrying FGF2 (MSCs-FGF2), compared with groups treated with MSCs alone. The histopathological index of LPS-induced lung injury was improved after MSCs-based FGF2 gene treatment. The MSCs-FGF2 administration also reduced the level of inflammatory cytokines. CONCLUSIONS These results suggest that MSCs and FGF2 have a synergistic role in the treatment of LPS-induced lung injury.