Canstatin, a cleaved product of type IV collagen α2 chain, was firstly identified as a potent endogenous anti-angiogenic factor. Although type IV collagen α2 chain is a major component of basement membrane in cardiomyocytes, expression and physiological role of canstatin in heart remain unclear. We previously showed canstatin has a variety of biological activities in cardiac cells. Here, we report the altered expression and cardioprotective effects of canstatin in experimental rat models for cardiac diseases. Canstatin was highly expressed in myocardium while it was decreased in the infarcted area after myocardial infarction. Administration of canstatin to the myocardial infarction model exerted protective roles by promoting scar tissue formation and inhibiting cardiac remodeling including hypertrophy and fibrosis in non-infarcted area. Canstatin attenuated ischemia/reperfusion-induced ventricular arrhythmia. Plasma canstatin concentration was decreased in monocrotaline-induced pulmonary hypertensive rat which was negatively correlated with the increase of right ventricular weight. Canstatin administration exerted protective effects against monocrotaline-induced right ventricular remodeling. These findings may contribute to the development of innovative drug and biomarker targeting canstatin for cardiac diseases.