The present study intended to observe the homing capability and therapeutic effect of CXC chemokine receptor 4 (CXCR-4) gene overexpressed bone marrow mesenchymal stem cells (BMSCs) on colitis, and to study the possible mechanisms involved. BMSCs were derived from male BALB/c mice and CXCR-4 gene was transfected into BMSCs by the utilization of the lentiviral vector. The expression of CXCR-4 gene was analyzed and the biological characteristics, and vitality of BMSCs and CXCR-4 gene overexpressed BMSCs (CXCR-BMSCs) were detected. The chemotaxis assay was performed to investigate migration . Colitis was induced by TNBS in female BALB/c mice. BMSCs and CXCR-BMSCs were injected into experimental models intravenously. The homing of cells was confirmed by fluorescence observation and Sry gene detection. Clinical manifestation and histological changes were also evaluated. The expression levels of occludin and vascular endothelial growth factor (VEGF) were detected to measure mucosal repair. Furthermore, CXCR-4 gene was successfully transfected into BMSCs by the utilization of lentiviral vector. Results indicated that overexpression of CXCR-4 gene did not influence the biological characteristics and vitality of BMSCs, but enhanced the capability of migration and homing of BMSCs and . Notably, CXCR-BMSCs had an improved effect on treating colitis, and the expression levels of Occludin and VEGF were higher. The results suggested that overexpression of CXCR-4 gene may enhance BMSC homing to damaged intestinal mucosa and their curative effect on colitis. The present findings indicated that using lentiviral vector to transfect CXCR-4 gene into BMSCs may be a potential method to improve the outcomes of BMSCs treatment on inflammatory bowel disease.