<p>The skin is the largest organ of the human body, capable of protecting it from external harm. However, due to trauma, paralysis, and other external factors, skin damage can occur, and scars may form. Exosomes have regenerative functions and, as a cell-free therapy, show great potential for wound healing. In this study, we aimed to investigate whether thrombin-preconditioned umbilical cord mesenchymal stem cells (T-pre-UCMSCs) increase the production of exosomes. Different umbilical cord mesenchymal stem cell exosomes can accelerate the healing of skin. In our study, umbilical cord mesenchymal stem cells (UCMCs) were cultured in DMEM/F12 medium without fetal bovine serum (FBS) for 72&#xa0;h with 200U/ml thrombin. Exosomes were isolated from the supernatant by ultracentrifugation. There are two kinds of exosomes: UCMCs culture supernatant–derived exosomes (UCMSCs-Exos) and T-pre-UCMSCs culture supernatant–derived exosomes (T-UCMSCs-Exos). The skin injury cell model was constructed by treating HaCats with a tip. Additionally, the wound healing capacity of exosomes was evaluated in vivo using a mouse skin injury model. Compared to UCMSCs-Exos, T-UCMSCs-Exos significantly promoted cell proliferation and migration of cells. In vivo experiments demonstrated that T-UCMSCs-Exos can accelerate wound closure and enhance collagen maturation, promoting angiogenesis in the vascularized wound area. These results indicate that T-UCMSCs-Exos have good potential for accelerating wound healing and minimizing scar formation. Our research indicates that thrombin pre-UCMSCs significantly increased the production of exosomes. These findings demonstrate that T-UCMSCs-Exos for skin wounds are a promising cell-free therapy that can be applied in the treatment of skin injuries.</p>