The purpose of this study was to investigate the effects of luteolin (Lu) on myocardial ischemia-reperfusion (I/R) injury in rats. I/R model was established by ligating left anterior descending branch of coronary artery in rats. Cardiac hemodynamic measurement, myocardial infarction and damage assessment, antioxidant enzymes activities analysis, and various biochemical indexes of myocardial tissue were measured. Finally, the expression of proteins levels of Siti1/NLRP3/NF-κB pathway of myocardial tissue in rat were measured by Western Blotting. Lu obviously reduced the myocardial infarction in rats. Compared with sham group, I/R rats showed significant increase in LDH and CK-MB levels. In Lu group, LDH and CK-MB in I/R rats significantly decreased. In addition, Lu significantly reduced leukocyte infiltration compared with the sham group. On the other hand, Lu pretreatment effectively decreased the levels of cytokines in serum. The Siti1/NLRP3/NF-κBpathway in I/R group was significantly imbalance that in I/R group. Lu significantly restored the above protein changes. Lu may reduce I/R by regulation of Sirt1/NLRP3/NF-κBpathway.Copyright © 2020 Elsevier B.V. All rights reserved.