Bone marrow mesenchymal stem cells (BM-MSCs) have therapeutic potential in acute lung injury (ALI). Hypoxia-induced mitogenic factor (HIMF) is a lung-specific growth factor that participates in a variety of lung diseases. In this study, we evaluated the therapeutic role of BM-MSC transplantation in lipopolysaccharide (LPS)- induced ALI and assessed the importance of HIMF in MSC transplantation. MSCs were isolated and identified, and untransduced MSCs, MSCs transduced with null vector or MSCs transduced with a vector encoding HIMF were transplanted into mice with LPS-induced ALI. Histopathological changes, cytokine expression and indices of lung inflammation and lung injury were assessed in the various experimental groups. Lentiviral transduction did not influence the biological features of MSCs. In addition, transplantation of BM-MSCs alone had significant therapeutic effects on LPS-induced ALI, although BM-MSCs expressing HIMF failed to improve the histopathological changes observed with lung injury. Unexpectedly, tumour necrosis factor α levels in lung tissues, lung oedema and leucocyte infiltration into lungs were even higher after the transplantation of MSCs expressing HIMF, followed by a significant increase in lung hydroxyproline content and α-smooth muscle actin expression on day 14, as compared to treatment with untransduced MSCs. BM-MSC transplantation improved LPS-induced lung injury independent of HIMF.