Aim To study the effects of phentolamine on myocardial extracellular matrix of cardiac remodeling induced by norepinephrine in rats. Methods Twenty-four male SD rats were randomly divided into control group, norepinephrine group （model group） and norepinephrine＋phentolamine group （treatment group）. Left ventricular structure and function among groups of rats were measured by echocardiography. Extracellular matrix remodeling was evaluated by morphological examination, stained with Van-Gieson （VG）. The content of hydroxyproline in the tissue of myocardium was measured. The protein expression of matrix metalloproteinase- 2 （MMP-2） and collagen Ⅰ were examined by immunohistochemical analysis. Results Compared with control group, left ventricular hypertrophy, the hydroxyproline content, collagen volume fraction （CVF） and protein expression of MMP-2 and collagen Ⅰ was significantly higher in the model group rats （P＜0.01）. In treatment group rats, myocardial hypertrophy obviously improved, hydroxyproline, CVF reduced, protein expression of MMP-2 and collagenⅠdecreased （P＜0.05）. Conclusion Phentolamine can prevent the cardiac hypertrophy and extracellular matrix remodeling, which was associated with the attenuation of myocardial MMP-2and collagen Ⅰ.