Background: No-reflow (NR) phenomenon is a risk factor which severely compromises the benefits of coronary revascularization in patients with acute myocardial infarction. It has been found that autophagy increased after IR, and it seems that modest levels of autophagy appear to be protective. Our previous researches showed that the myocardial IR caused significant change of polyamine metabolism, and exogenous spermine protected the neonatal rat cardiomyocytes against anoxia-reoxygenation injury (ARI). The present study was undertaken to see whether exogenous spermine had protective effects against acute myocardial IR injury in vivo rat model, whether it reduced the myocardial no-reflow size and whether autophagy were involved in the protective effect. Methods: Thirty SD rats weighing 250-300g were equally randomized to three groups: Sham control group, where the rats were treated with thoracotomy only; ischemia reperfusion (IR) group, where the rats were treated with ischemia for 40 min and reperfusion for 60 min; and spermine (SP) group, where 0.5mmol/L spermine (2ml/kg, i.v.) were given just 15min before reperfusion. The cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) activities in serum were determined. NR size of the myocardium was measured by using Evan’s blue and thioflavin S staining. Inflammatory response was detected by myocardial tissue myeloperoxidase (MPO) assay. And autophagy function was detected by measuring expression of Beclin-1 through Western blot. Results: Spermine decreased serum cTnI and CK-MB levels, and reduced the IR-induced NR size of the left ventricle. Tissue MPO assay showed that myocardial inflammatory response was attenuated by spermine compared with IR. Western blot showed that Beclin-1 was up-regulated by spermine compared with IR group. Conclusion: By up-regulating autophagy, exogenous spermine attenuated inflammatory response during myocardial IR, which contributed to reduce IR-associated NR size. Therefore, exogenous spermine or induce endogenous spermine might be a promising approach to prevent NR in patient with acute myocardial infarction (AMI) underwent reperfusion. Animal care All animal experiments were approved by the Animal Research Ethics Committee of the Wenzhou Medical College, Wenzhou, China. The investigation conformed with the guide for the care and use of laboratory animals published by the US National Institutes of Health. The whole procedures were performed under anaethesia.