〔Abstract〕 Objective To observe the effect of spermidine on the expression of connexin 43 (Cx43) in the myocardium of rats with myocardial infarction, and to analyze the corresponding myocardial protective mechanisms simultaneously. Methods Twenty-four male SD rats were randomly divided into sham operation group, myocardial infarction model group, and model + spermidine group, with 8 rats in each group. An animal model of acute myocardial infarction was successfully constructed through in vivo ligation of the anterior descending coronary artery. The rats in the sham operation group passed the line 2 mm below the left atrial appendage without ligation, and the other operations were the same as those in the myocardial infarction model group. The rats in sham operation group and the myocardial infarction model group were given ordinary drinking water for 4 weeks after surgery, the rats in the model + spermidine group underwent surgery were given drinking water containing spermidine (concentration 5 mmol·L-1) for 4 weeks. Immunohistochemistry was used to detect the distribution characteristics of Cx43 in each group.Western blotting was used to detect the protein expression levels of Bcl2-associated X protein (Bax), B lymphoma-2 gene (Bcl-2), Caspase-3 and Cytochrome C. Results The Cx43 optical density value of the myocardial infarction model group was significantly lower than that of the sham operation group, and the difference was statistically significant (P < 0.05). Compared with the myocardial infarction model group, The Cx43 optical density value of the model + spermidine group was significantly increased, and the difference was statistically significant (P < 0.05). The positive expression of Cx43 in the intercalary disc increased significantly in the model+spermidine group, and the distribution pattern was close to that of the sham operation group. Compared with the sham operation group, the protein expression levels of Bax, Caspase-3 and Cytochrome C in the myocardial infarction model group were significantly increased, and the expression level of Bcl-2 protein was significantly decreased, the differences were statistically significant (P < 0.05). Compared with the myocardial infarction model group, the protein expression levels of Bax, Caspase-3 and Cytochrome C in the model + spermidine group were significantly reduced, and the differences were statistically significant (P < 0.05), but there was no statistical difference in the expression levels of Bcl-2 protein between the two groups (P > 0.05). Conclusion Spermidine can inhibit Cx43 expression, reduce arrhythmia, inhibit myocardial cell apoptosisand and protect myocardium in rats with myocardial infarction.