Myocardial infarction is a common cause of disability. Decorin is a myokine that has anti-inflammatory, anti-apoptotic effects. Some studies stated that decorin protects myocardium from ischemia. Other studies stated that decorin levels are associated with acute coronary syndrome. The study aimed to investigate the therapeutic role of decorin on cardiac function in a rat model of myocardial infarction. Thirty adult male Wistar rats were divided into control group-rats were subcutaneously injected with normal saline, isoprenaline-injected group-rats were subcutaneously injected with isoprenaline (85 mg/kg) once daily for 2 days to induce myocardial infarction, and decorin ± isoprenaline-injected group-rats were injected as the previous group, followed by decorin injection (0.1 mg/kg) once daily for 7 days. Cardiac hemodynamics, serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), oxidative stress markers, gene expression for myocardial-transforming growth factor beta 1 (TGF-β1), interleukin 1 b (IL-1β), tumor necrosis factor alpha (TNF-α), and cardiac caspase-3 immunohistochemical analysis were done. Isoprenaline + decorin group had significant improvement in cardiac hemodynamics and oxidative stress markers; significant decrease in serum CK-MB, LDH, and myocardial gene expression for TNF-α, IL-1β, and TGF-β1; and decreased cardiac caspase-3 immunoreactivity was present. Therefore, decorin can be used as a therapeutic agent after myocardial infarction as it improved the cardiac function.