〔Abstract〕 Objective To explore the effect of miRNA-222-3p in endothelial progenitor cell-derived exosomes(EPCs-Exo) on skin wound healing in diabetic mice. Methods Endothelial progenitor cell(EPCs) derived from C57BL/6 mouse bone marrow were identified by fluorescence staining.Subsequently, EPCs-Exo isolated from the media of EPCs were identified, and high-throughput sequencing of EPCs-Exo miRNA was completed.The skin injury model of diabetic mice was established.According to different groups, the wounds were treated with externally applied phosphate buffer solution(PBS) and EPCs-Exo; Subcutaneous injection of PBS,agomiR-222-3p, and antagomiR-222-3p at the edge of the wound was performed continuously for 14 days, and the wound healing rate was observed.Meanwhile, immunofluorescence methods were used to investigate the changes in the expression levels of ROS,CD31,and VEGF in the wound margin tissue before and after treatment. Results EPCs-Exo significantly accelerated skin wound healing in diabetic mice, reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05). High-throughput sequencing showed that miRNA-222-3p was highly expressed in EPCs-Exo.Local subcutaneous injection of miRNA-222-3p into wound margin tissue significantly promoted the skin wound healing of diabetic mice, reduced the level of ROS,and increased the expression level of VEGF and CD31 in the wound margin tissue(P<0.05). Conclusion MiRNA-222-3p promotes wound healing in diabetic mice and plays an important role in EPCs-Exo promoting wound healing.