Background: Chronic heart failure (CHF) is the end result of the majority of cardiovascular diseases and despite the progress in treatment methods during the past two decades, its total morbidity and mortality remains high. Low serum vaspin level is associated with an increase of major adverse cardiac events risk, however, to date; no studies have been elaborated to determine the effects of vaspin administration on heart failure (HF). Objective: This study was conducted to examine the possible protective effects of vaspin on isoproterenol-induced chronic heart failure in rats and to explore the possible related mechanisms. Materials and methods: Thirty healthy adult male albino rats of initial body weight 215-241 g were included in the study. Rats were randomly and equally divided into 3 groups: Group (I): vehicle treated control group, group (II): experimental isoproterenol-induced HF group, and group (III): experimental isoproterenol-induced HF treated by vaspin group. Rats were examined for echocardiographic evaluation of heart function, the serum levels of lactate dehydrogenase (LDH), creatine phosphokinase-muscle/brain (CPK-MB) and cardiac troponin I (cTnI) and cardiac superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), nitric oxide (NO) as well as the levels of cardiac tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Histopathological examination for cardiac tissues was also evaluated under Haematoxylin and Eosin and Masson’s Trichome stains. Results: The present study revealed that vaspin administration significantly improved the increased serum LDH, CPK-MB and cTnI, cardiac TNF α, IL 6 and MDA, left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), heart weight and heart weight index observed in isoproterenol-induced CHF group. It also improved the decreased activity of cardiac SOD, CAT and GPx, cardiac NO, left ventricular fractional shortening (LVFS) as well as left ventricular ejection fraction (LVEF). Moreover, it improved cardiac hypertrophy and the myofibrillar degeneration and fibrosis observed in histopathological examination in isoproterenol-induced CHF group. Conclusion: The results of the current study indicated that vaspin inhibited the progression of cardiac degeneration, fibrosis and HF in experimental isoproterenol-induced CHF in rats. Key words: cardiomyopathy, heart failure, vaspin, inflammation.