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We studied the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of paraquat-indueed acute lung injury in SD rats.Stromal cell-derived factor-i (SDF-1) and its receptor CXCR4 has been shown to participate in mobilizing MSCs.We used adenovirus carrying CXCR4 gene to transfect MSCs to increase engraftment numbers of MSCs at injured sites.Histological examination data demonstrated that engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis.We found that engraftment of MSCs almost differentiated into myofibroblasts,rarely differentiated into lung epithelial cells.In the following research, we demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated myofibroblast differentiation of MSCs in vivo.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 aberrant activated Wnt signaling induces myofibroblasts differentiation of engrafted MSCs to contribute pulmonary fibrosis after lung injury.