Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 has been shown to participate in mobilizing bone marrow-derived mesenchymal stem cells (MSCs).We studied the effects of MSCs in a model of HCI induced acute lung injury in SD rats by modulating the SDF-1/CXCR4 axis.After intranasal instillation of HCI, SDF-1 levels in serum and lung tissue lysates were increased.We used adenovirus carrying CXCR4 gene to transfect MSCs in order to increase engraftment number of MSCs at injured sites.Immunohistochemical staining and flow cytometry analysis indicated that SDF-1/CXCR4 axis indeed improved numbers of exogenous MSCs transplanted in injured lung.However, engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis.We found that engraftment of MSCs almost differentiated into lung fibroblasts or myofibroblasts, rarely differentiated into lung epithelial cells.In the following research, we demonstrated that canonical Wnt/β-catenin signaling was activated in injured tissue and may be involved in regulating the differentiation of MSCs.In vitro study, we demonstrated that activation of the Wnt/ β-catenin signaling, could stimulate MSCs to express myofibroblasts markers, but this process was attenuated by Wnt antagonists DKK1.Our data demonstrated that SDF-1/CXCR4 axis is important in regulating migration of MSCs for lung repair or pulmonary fibrogenesis.Wnt signaling plays a key role in the regulation of MSCs differentiation and the pathogenesis of fibrotic diseases.We suggested that abnormal activated Wnt signaling would play an important role in pulmonary fibrosis by inducing myofibroblasts differentiation of MSCs.