Growth hormone-releasing peptides (GHRP) are a class of synthetic peptidyl growth hormone secretagogues (GHS) that have been reported to exert a cardioprotective effect on cardiac ischemia. However, it is unclear whether GHRP have any beneficial effect on chronic heart failure (CHF). The present work aims to clarify this issue. Pressure-overload CHF was created by abdominal aortic banding in the rat. Nine weeks after surgery, one of four variants of GHRP (GHRP-1, -2, -6 and hexarelin, 100 µg/kg) or saline was injected subcutaneously twice a day for three weeks. Echocardiography and cardiac catheterization were performed to monitor cardiac function and obtain blood samples for hormone assay. GHRP treatment significantly improved left ventricular (LV) function and remodeling in CHF rats, as indicated by increased LV ejection fraction, LV end-systolic pressure and diastolic posterior wall thickness, and decreased LV end-diastolic pressure and LV end-diastolic dimension. GHRP also significantly alleviated the development of cardiac cachexia, as shown by the increases in body weight and tibial length in CHF rats. Plasma catecholamine, renin, angiotensin II, aldosterone, endothelin-1 and atrial natriuretic peptide were significantly elevated in CHF rats but were significantly decreased in CHF rats treated with GHRP. GHRP suppressed cardiomyocyte apoptosis and increased cardiac GHS receptor mRNA expression in CHF rats. GHRP also decreased myocardial creatine kinase release in hypophysectomized rats subjected to acute myocardial ischemia. We conclude that chronic administration of GHRP alleviates LV dysfunction, pathological remodeling, and cardiac cachexia in CHF rats at least in part by suppressing stress-induced neurohormonal activations and cardiomyocyte apoptosis.