Objective To examine the effect of Astragalus (AS) injection on post-myocardial infarction-inducedcardiac remodeling in rats, and explore potential mechanisms underlying such effects. Methods A cardiac remodelingpost-myocardial infarction model was prepared in rats, which were divided into four groups: sham operation, myocardialinfarction (model group), low-dose AS (ASL, 1 mL/ kg), and high-dose AS (ASH, 3 mL/ kg). Survival rate of the ratsand activities of the alpha isoform of myosin heavy chain (α-MHC) and N-terminal pro b-type natriuretic peptide (NTproBNP)in rat serum were measured after 6-week treatment. Histopathological changes and myocardial fibrosis wereobserved by light microscopy using hematoxylin and eosin, and Masson trichome staining. Quantification of malondialdehyde(MDA), nitric oxide ( NO), and endothelial nitric oxide synthase ( eNOS) were carried out using enzyme-linkedimmunosorbent assays. Protein expression of phosphatidylinositol 3 kinase (PI3K), phosphorylated AKT (p-AKT), and peNOSwere analyzed by western blotting. Results Compared with the model group, the survival rate of the ASL and ASHgroup were increased, but not significantly ( P > 0. 05). Meanwhile, α-MHC and NT-proBNP contents in the ASH groupwere reduced ( P < 0. 05). In addition, inflammation, hyperemia, and interstitial fibrosis were reduced in the ASH group.Moreover, the ASH group exhibited increased protein expression of PI3K and p-AKT in the injured heart ( P < 0. 05). peNOSexpression in the ASH group was increased compared with the model group ( P < 0. 05). Conclusions AS elicits anobvious protective effect on cardiac remodeling after myocardial infarction in rats. Activation of the PI3K/ AKT pathway mayactivate p-eNOS, which is involved in the mechanism by which AS prevents oxidative stress during cardiac remodeling.