Abstract: Objective: To investigate the effect of Panax notoginseng total saponins(PNS)compound nano-vesicles on skin wound healing and vascular formation in diabetic foot ulcer (DFU) rats.Methods: Male SD rats were used to construct DFU models.Twenty-seven rats with successful DFU models were randomly divided into a DFU group, a PNS group and a PNS compound nano-vesicles(PNS-CNV)group, with 9 rats in each group.Another 12 rats with normal blood glucose levels and skin wounds were taken as Control group.The wound healing rate of each group was compared.Serum levels of inflammatory cytokines interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA); histopathological changes in the wound tissues were evaluated using hematoxylin and eosin(HE)staining.Microvessel density (MVD) in the wound tissues was assessed using immunohistochemical staining; protein expression of vascular endothelial growth factor(VEGF)and neurogenic locus notch homolog protein 1(Notch1)in the wound tissues was determined using western blotting.Results: After modeling, the fasting blood glucose (FBG) levels of rats in the DFU group, PNS and PNS-CNV groups were higher than those in the Control group (P< 0.05); on the 7th and 14th day of drug intervention, compared with the DFU group, the FBG of rats in the PNS and PNSCNV groups was significantly reduced, and the PNS-CNV group was lower than the PNS group (both P< 0.05).Compared with the Control group, rats in the DFU group showed significant decreases in wound healing rate, CD34 positive expression in the wound tissues, MVD, and VEGF protein expression, while the levels of IL-6, IL-8, TNF-α in serum and Notch1 protein expression in the wound tissues were increased(both P< 0.05).Compared with the DFU group, rats in the PNS and PNS-CNV groups exhibited increases in wound healing rate, CD34 positive expression in the wound tissues, MVD, and VEGF protein expression, while the levels of IL-6, IL-8, TNF-α in serum and Notch1 protein expression in the wound tissues were decreased (all P< 0.05).Compared with the PNS group, rats in the PNS-CNV group showed increases in wound healing rate, CD34 positive expression in the wound tissues, MVD, and VEGF protein expression, while the levels of IL-6, IL-8, TNF-α in serum and Notch1 protein expression in the wound tissues were decreased (all P< 0.05).Conclusion: PNS-CNV can up-regurate the expression of VEGF in the wound tissues of DFU rats, inhibit inflammation, promote vascular formation, thus accelerating wound healing, which is better than PNS.