Objective To investigate the effect of astragaloside Ⅳ (ASⅣ) on wound healing in rats with deep second-degree burns via the Notch receptor 1(Notch1) / Twist-related protein 1 ( Twist1) signaling pathway. Methods Sprague-Dawley rats were assigned randomly into Con group, Model group, L-ASⅣ ( low-dose ASⅣ) group, H-ASⅣ (high-dose ASⅣ) group, MEBO (positive control drug: moist exposed burn ointment) group, and DAPT (high-dose ASⅣ+Notch1 inhibitor DAPT) group ( n= 15 rats per group). Deep second-degree burns were established in all groups except the Con group. The healing rate and moisture content of burn wounds were detected and serum levels of interleukin ( IL)-8, IL-18, and IL-6 were measured in each group. Histopathological and apoptotic changes in burn-wound tissues were measured and expression levels of basic fibroblast growth factor ( bFGF), epidermal growth factor ( EGF), vascular endothelial growth factor ( VEGF), platelet endothelial cell adhesion molecule (CD31), and Notch1 / Twist1 pathway proteins in burn-wound tissues were also measured in each group. Results Compared with Con group, rats in Model group showed clear edema, structural integrity damage, and inflammatory cell infiltration in the burn-wound tissue, increased water content, IL-8, IL-18, IL-6, apoptosis rate, and average fluorescence intensities of EGF and b-FGF, and decreased average optical densities of VEGF and CD31 and Notch1 and Twist1 protein expression levels (P< 0. 05). Compared with Model group, rats in L-ASⅣ group, H-ASⅣ group, and MEBO group showed reduced tissue edema and inflammatory cell infiltration in burn wounds, restored structural integrity, increased wound-healing rate, average fluorescence intensities of EGF and bFGF, average optical densities of VEGF and CD31, and expression levels of Notch1 and Twist1, and decreased water content, IL-8, IL-18, IL-6, and cell apoptosis rate (P<0. 05). Compared with H-ASⅣ group, rats in DAPT group showed increased tissue edema and inflammatory cell infiltration in burn wounds, structural integrity damage, reduced wound-healing rate, average fluorescence intensities of EGF and b-FGF, average optical densities of VEGF and CD31, and expression of Notch1 and Twist1, and increased water content, IL-8, IL-18, IL-6, and cell apoptosis rate (P<0. 05). Conclusions ASⅣ may promote wound healing in rats with deep second-degree burns by activating the Notch1 / Twist1 signaling pathway.