The disclosure provides a mesenchymal stem cell (MSC) over-expressing CXCR5, preparation method and use thereof. Overexpression of CXCR5 can allow directed migration of MSCCXCR5 to an inflammation area in vivo so as to play a role in immunomodulation but not make MSCCXCR5 randomly scattered at various parts in a body. Treatment of diseases using the mesenchymal stem cells will have more targeting and effectiveness, and will effectively improve the treatment effect of MSC.
