In this experiment, we explored the role of astragaloside in regulating Egr-1 through S14G-humanin on asthmatic airway inflammation. 64 juvenile Sprague Dawley (SD) rats were selected. After establishing rat asthma model, they were assigned into blank control group, astragaloside group, S14G-Humanin group and astragaloside+S14G-Humanin group (combined group). Astragaloside group was intervened with astragaloside II 0.6 mg/kg, S14G-Humanin group was intervened with 50 μm S14G-Humanin, combined group RBSMCs were treated with astragaloside II 0.6 mg/kg and 50 μM S14G-Humaninn. Airway responsiveness was assessed and pathological damage of lung tissue was assessed by HE staining along with analysis of inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory cytokines and bone-marrow derived mesenchymal stem cells (rBMSCs) behaviors. Compared to blank control, the Penh values of astragaloside group, S14G-Humanin group and combination group were increased (P <0.05) and pathological scores were lower with the lowest score in combined group (all P <0.05). The number of white blood cells, neutrophils, eosinophils, macrophages and lymphocytes in BALF of rats in astragaloside group, S14G-Humanin group and combination group were decreased, with the lowest number in combination group (P <0.05). In addition, IL-4, IL-6, and IL-21 in astragaloside group, S14G-Humanin group and combination group were reduced, with the lowest levels in combination group (P <0.05). RBSMCs proliferation and migration ability in treatment group was reduced with the lowest in combination group (P <0.05). After up-regulating S14G-Humanin, Egr-1 mRNA expression was elevated (P <0.05). Astragaloside can reduce inflammatory cells and inflammatory cytokines and increase the expression of Egr-1 by regulating S14G-Humanin expression.