This study's objective is to analyze the effect of epidermal growth factor (EGF) nanoparticles on the healing of diabetic skin wounds and also, simultaneously, to investigate the mechanism of EGF nanoparticles to promote healing. In this manuscript, EGF nanoparticles were prepared, and also the drug loading rate of EGF nanoparticles was measured. In the meantime, a diabetic skin wound model was prepared with the use of rats. Then, the rats were split into four groups: EGF nanogroup, EGF group, empty particle group, and control group. Additionally, the results indicate that this study was successful in preparing EGF nanoparticles with a stable performance, and the drug was released for 24 hours. The wound healing in the EGF nanoparticle group was quicker than that in the EGF group. Furthermore, the area of EGF receptor-positive cells in the wound surface of the EGF nanogroup was higher than that of the EGF group, with the results demonstrating that EGF nanoparticles upregulated the expression of EGF receptors in wound surface cells, promoted wound surface healing, and had better efficacy than EGF.