A skin flap is a piece of skin that has its own blood supply, which is useful to repair large skin defects and deep wounds in plastic surgery. However, partial skin flap necrosis usually occurred. Bone marrow mesenchymal stem cells (BM MSCs) are effective in improving the ischemic flap survival, but their clinical application is restricted by their limited source. Human umbilical cord matrix stem (HUCMS) cells are easily isolated in a large number, compared to BM MSCs. In this study, we evaluated the therapeutic potential of HUCMS to improve the survival of ischemic skin flap. HUCMS cells were characterized with surface markers, and were labeled with 5-acetylene base-2 'deoxidizing uracil nucleoside (EdU) in vitro. Twenty male immunodeficient BALB/c mice with an epigastric flap were randomly divided into two groups. HUCMS cells or Dulbecco's Modified Eagle Medium (DMEM) were injected into the subcutaneous flap tissues. On the 7th postoperative day, flap survival, capillary density, levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and EdU-positive cells in the skin flap were examined. Results showed that flap survival rate was higher in the HUCMS cell group (P < 0.05). Capillary density, VEGF level, and bFGF level were higher in the HUCMS cell group (P < 0.05). EdU-labeled HUCMS cells were mainly distributed in the subcutaneous flap tissues. These findings suggest that HUCMS cells can improve the survival of ischemic skin flap by promoting vascularization, which may be attributed to the increased expression of VEGF and bFGF.