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Objective: To explore the potential active ingredients and targets of Astragalus, and also to predict the targets and mechanisms of Astragalus in the treatment of diabetic cardiomyopathy. Based on the predicted results, the key signaling pathways were validated in a diabetic cardiomyopathy model mouse.Methods: Compounds and targets in Astragalus were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The protein names to corresponding "Gene Symbol ID" was convert by STRING database.We obtained targets of diabetic cardiomyopathy data from DisGeNET datasets. The protein-protein interaction network (PPI network) was established using STRING database. Cytoscape 3.6.0 was used to construct a disease-drug-target gene network map and to screen the 10 closest target genes by Cytohuba plug-in. The overlapping genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)-based enrichment analysis.Finally, the key molecules of the MAPK signaling pathway were validated by in vitro experiments. Animal experiments were performed using 21 Kunming mice randomly divided into normal group, model group, and Chinese herbal medicine Astragalus group, with seven mice in each group. The myocardium of mice in each group was stained with HE to compare the pathological morphological changes, and Western Blot was also used to compare the key molecules of MAPK signaling pathway, ERK1 and p-p38. Results: Astragalus contained 20 active ingredients with 188 corresponding targets, 220 targets related to diabetic cardiomyopathy and 37 targets acting in conjunction with Astragalus. The common targets were imported into the STRING database to obtain a PPI network graph of overlapping genes, with 37 nodes and 391 edges. The PPI network map was imported into Cytoscape 3.6.0 software, and the most significant top 10 hub genes were obtained using the MCC algorithm in the cytoHubba plugin, namely AKT1,TP53,CASP3,MMP9,EGF,IL-10, CXCL8,IL-1β,VEGFA,PPARG. GO functional enrichment analysis yielded 40 entries for biological process (BP), 23 entries for cellular component (CC), 22 entries for molecular function (MF) and 94 entries for KEGG pathway enrichment screening, mainly involving PI3K-AKT, MAPK, HIF-1, FOXO, TNP pathway and other inflammation or apoptosis regulatory pathways. Animal experiments showed that Astragalus can improve the inflammatory state of myocardial tissue in mice with diabetic cardiomyopathy, and the expression of ERK1 and p-p38 protein in myocardial tissue of mice in the model group was higher than that in the normal group (P<0.05, P<0.01), and after the intervention with Astragalus, the expression of ERK1 and p-p38 protein was significantly lower than that in the model group, and the difference was statistically significant (P<0.05, P<0.01). Conclusion: Astragalus has multi-target, multi-component and multi-pathway action characteristics in the treatment of diabetic cardiomyopathy, which can exert anti-inflammatory and anti-oxidative stress effects by regulating protein expression of MAPK signaling pathway ERK1, p-p38. [ABSTRACT FROM AUTHOR]