Recent studies have suggested that the prevention of myocardial infarction (MI) through diet is very important and that the intake of polyphenol-rich foods can improve cardiovascular health. In this study, adult male SD rats were randomly divided into 2 groups. The chlorogenic acid (CGA) group (n = 18) was administered 100 mg/kg/day CGA by gavage, and the control (CON) group (n = 18) was given the equivalent volume of water for 4 weeks. A model of MI was established by ligating the left anterior descending (LAD) coronary artery, which was monitored by an electrocardiogram (ECG). Blood samples were analyzed by enzyme-linked immunosorbent assays and biochemical experiments 24 h after the operation. In addition, histopathological analysis was performed to assess the size and severity of the infarct area. The administration of CGA before MI minimized weight gain and was associated with decreased postoperative mortality. CGA moderated the coronary artery ligation-induced changes observed by ECG and decreased the plasma levels of the myocardial markers. In the histopathological analysis, CGA notably reduced infarct size and decreased myocardial injury and fibrosis. Furthermore, CGA significantly reduced the levels of pro-inflammatory factors, and this reduction was accompanied by an upregulation of anti-inflammatory cytokines and an increase in antioxidant enzyme activities. This study indicated that CGA improved the survival rate after MI and demonstrated that CGA had a protective effect on MI by reducing the inflammatory response and exerting antioxidant activity.Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.