To investigate the effects of interleukin-6 (IL-6) gene knockout on myocardial remodeling after myocardial infarction (MI) in mice and the potential mechanism, to provide certain references for the prevention and treatment of MI in clinic.A total of 40 male C57 mice were divided into two groups, namely Sham group (n=20) and MI group (n=20), using a random number table. Another 20 mice with IL-6 gene knockout were enrolled into the MI + IL-6 KO group. The MI model was established by means of ligating the left anterior descending coronary artery of the mice. 28 d later, the survival status of the three groups of mice was recorded. In addition, the cardiac functions of each group of mice, including two-dimensional echocardiography, ejection fraction (EF%) and fractional shortening (FS%), were measured. The cross-sectional area and pathological change of the myocardial cells in cardiac tissues of each group of mice were detected via hematoxylin and eosin (HE) staining. Immunohistochemistry was applied to determine the expression of tumor necrosis factor-alpha (TNF-α) in each group of mouse cardiac tissues. Moreover, immunofluorescent staining was utilized to measure the content of M2 macrophages in each group of mouse cardiac tissues.The 28-d survival rate of the mice with IL-6 gene knockout was remarkably higher than that of the wild-type mice (p0.05). Furthermore, the cardiac functions of the mice in the MI + IL-6 KO group were superior to those in the MI group, with markedly improved FS% and EF% (p0.05). According to the HE staining results, the cross-sectional areas of the heart and myocardial cells were decreased notably in MI + IL-6 KO group compared with those in the MI group (p0.05). The immunohistochemical staining results showed that IL-6 knockout could lower the MI-induced high expression of TNF-α (p0.05), and Masson's trichrome staining indicated that IL-6 knockout could also repress the degree of cardiac fibrosis. Moreover, it was discovered through immunofluorescent staining that the mice in the MI + IL-6 KO group had markedly elevated content of M2 macrophages in cardiac tissues than those in the MI group (p0.05).Inhibiting IL-6 gene expression can prominently ameliorate the MI-induced myocardial remodeling, whose mechanism is possibly associated with the activation of M2 macrophages and reduced collagen production in fibroblast cells.