Objective This study was to investigate the effects of trimethylamine N⁃oxide（TMAO）on cardiac function and macrophage polarization in mice with myocardial infarction（MI）. Methods Male C57BL/6 mice were randomly divided into the Sham，MI，and MI+TMAO groups. For the MI model，mice were subjected to permanent left anterior descending ligation. After the surgery，mice in the MI+TMAO group were fed high choline diet，while those in the Sham and MI groups were fed chow diet. Twenty⁃one days later，serum TMAO levels and the levels of CK⁃MB and cTnT were detected. The infarct size of myocardial tissue was detected by Masson staining，and the expression of apoptotic cells was detected by TUNEL staining. Echocardiography，WGA staining and NT ⁃ proBNP were used to analyze the degree of cardiac function and hypertrophy. Immunofluorescence staining was used to detect the expression of Cx43. Furthermore，the expressions of serum inflammatory factors（IL⁃6，TNF⁃α）were detected by Elisa. RT⁃qPCR was used to detect M1 macrophage markers（IL⁃6，TNF⁃α and INOS）and M2 macrophage markers （CD206，IL⁃10 and TGF⁃ β）in myocardial tissues，respectively. Results （1）High choline diet significantly increased plasma TMAO levels in MI mice，and TMAO promoted infarction size and myocardial enzymes as well as apoptosis in MI mice.（2）TMAO limited cardiac function and promoted ventricular hypertrophy in MI mice.（3）The results of Cx43 immunofluorescence staining indicated that TMAO significantly reduced the connection integrity between cardiomyocytes.（4）The mRNA levels of M1 macrophage markers in MI + TMAO group were significantly higher than those in MI group. On the contrary，the mRNA levels of M2 macrophage markers CD206，IL⁃10 and TGF ⁃β were significantly reduced in MI + TMAO group compared with MI group. Conclusion TMAO aggravated myocardial tissue injury and ventricular remodeling in MI mice by promoting M1⁃type macrophage polarization.