Seawater immersion can increase the damage to skin wounds and produce chronic wounds, and the application of human adipose-derived stem cells can significantly promote healing. However, the mechanism underlying angiogenesis is currently unclear. In this study, we investigated the vascularization effect of human adipose-derived stem cells on the repair of seawater-treated skin wounds and explored the underlying mechanisms using bioinformatics. The results showed that human adipose-derived stem cells differentiated into vascular endothelial cells and promoted seawater-immersed wound vascularization by promoting vascular endothelial cell proliferation and migration. The differentially expressed genes between human adipose-derived stem cells and fibroblasts were identified and analyzed (including via gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, protein–protein interaction network, and correlation analyses). The genes may promote wound healing by regulating the mechanisms of extracellular matrix remodeling, programmed cell death, inflammation, and vascularization. In conclusion, this study provides novel insights into the use of human adipose-derived stem cells in the regeneration of seawater-immersed skin wounds and chronic wounds.