Aim To explore the effect of phenylephrine(PE,α₁-adrenergic receptor agonist) on myocardial fibrosis induced by abdominal aorta coarctation (AAC) in mice and to elucidate related mechanism. Methods In this study,mice model of myocardial fibrosis were established by abdominal aorta coarctation in 28 mice, and 14 mice were randomly taken as control group and sham group. Eight weeks after surgery, mice were divided into 4 groups:AAC group, AAC+PE group (phenylephrine 0.65 mg/(kg·d) intraperitoneal injection),AAC+ Praz group (prazosin 5 mg/(kg·d) gavage) and AAC+Prop group(propranolol 10 mg/(kg·d) gavage). After administrated therapy for 4 weeks, the morphological changes of cardiac tissue were observed by hematoxylin-eosin (HE) staining, collagen volume fractions (CVF) of left ventricle were observed by Van-Gieson (VG) staining and hydroxyproline concentration were studied. The protein content of collagenⅠand collagen Ⅲ were examined by immunohistochemical analysis. Western blot was used to measure the myocardial protein expression of α-smooth muscle actin(α-SMA), transforming growth factor-β₁ (TGF-β₁), phosphor-drosophila mothers against decapentaplegic protein 2 (p-Smad2) and phosphor-drosophila mothers against decapentaplegic protein 3 (p-Smad3). Results Compared with control group, the heart of AAC group were developed fibrosis obviously. The CVF level and myocardial hydroxyproline concentration was significantly higher in AAC group as the same as protein level of collagenⅠand collagen Ⅲ (all P<0.01), and the protein expressions of α-SMA, TGF-β₁, p-Smad2 and p-Smad3 were also elevated (all P<0.01). PE treatment significantly reduced the CVF, hydroxyproline concentration, decreased expression of collagenⅠand collagen Ⅲ and expressions of α-SMA ,TGF-β₁, p-Smad2 and p-Smad3 in myocardial tissue compared with the AAC group (all P<0.05) as the same as propranolol treatment. However, prazosin had no effect on protein levels of α-SMA, TGF-β₁, and p-Smad3, although a small reduction in p-Smad2 levels was observed. Conclusion These data suggest that phenylephrine was as effective as propranolol to attenuate myocardial fibrosis induced by coarctation of abdominal aorta in mice, which may be associated with suppressing the TGF-β₁/Smads signal pathways.