BACKGROUND: Mesenchymal stem cells have great potential in the treatment of ischemia-reperfusion injury of skin flaps. However, their defects and the decline of their role in the treatment of ischemia-reperfusion injury of skin flaps restrict their wide application. OBJECTIVE: To review the strategies for improving the treatment of ischemia-reperfusion injury of skin flaps with mesenchymal stem cells, and provide a reference for its further theoretical research and clinical application. METHODS: Relevant documents included in CNKI, WanFang and PubMed were searched. The Chinese and English search terms were “mesenchymal stem cell, ischemia-reperfusion adjustment of skin flap, mesenchymal stem cells, stem cells, skin flap, ischemia-reperfusion injury, pretreatment, gene modification, biomaterial packaging, joint application”. The relevant documents since 2007 were retrieved, and the documents with little relationship between the research content and the article theme, poor quality and outdated content were eliminated through reading the article, and finally 75 documents were included for summary. RESULTS AND CONCLUSION: (1) Mesenchymal stem cells can inhibit inflammatory reactions, resist oxidative stress and induce angiogenesis, which has great potential in the treatment of skin flap ischemia-reperfusion injury. (2) Although mesenchymal stem cells have shown great potential in the treatment of skin flap ischemia-reperfusion injury, their shortcomings in treatment have limited their widespread clinical application. Through pre-treatment (cytokines, hypoxia, drugs, and other pre-treatment mesenchymal stem cells), gene-modified mesenchymal stem cells, biomaterial encapsulation of mesenchymal stem cells, as well as the combined use of mesenchymal stem cells and other drugs or therapeutic methods, can not only overcome the shortcomings of mesenchymal stem cells in treatment, but also improve their therapeutic effectiveness in skin flap ischemia-reperfusion injury. (3) Therefore, further improving the effectiveness of mesenchymal stem cells in treating skin flap ischemia-reperfusion injury and exploring its therapeutic potential are of great significance for the research of mesenchymal stem cells and the treatment of skin flap ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]