Background: Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction. B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes. Methods: The animal experiment used ligation of the left anterior descending (LAD) artery of C57BL/6 mice to establish a mouse acute myocardial infarction (AMI) model to observe changes in activated B cells and cytokines at different time points. Twelve-week-old C57BL/6 male mice were randomly divided into the Sham group (24 mice) (thread under the LAD artery without ligation) and the AMI group (64 mice). In addition, C57BL/6 B-cell knockout (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte cytokines, such as TNF-α IL-1β, IL-6, TGF-β1, COL1-A1, COL3-AIII, TIMP, and MMP9. Moreover, pathological and collagen changes in the myocardium were analysed. One-way ANOVA and LSD method was used for comparisons of multiple and pairwise groups respectively. P < 0.05 indicated significant differences. Results: An AMI model of C57BL/6 mice was established successfully. The ratio of activated B cells and the expression of TNF-α, IL-1β, IL-6, TGF-β1, and B cell activating factor (BAFF) in the 5-day subgroup were the highest in the myocardium, spleen and peripheral blood with the most obvious myocardial inflammatory cell infiltration. The cytokines mRNA expression levels in the 5-day subgroup of the BKO group were decreased compared with those in the WT group (P < 0.05). Among the 2-week subgroups of the Sham, WT and BKO groups, the the LVEDd and LVESd of the BKO group were lower than those of the WT group (P < 0.05), and the left ventricular ejection fraction was higher than that of the WT group (P < 0.05). Conclusion: Activated B cells participate in the sustained state of myocardial inflammation and immune system activation after AMI, and may affect the metabolism of myocardial collagen after AMI by secreting cytokines. Moreover, B cells promote the expression of myocardial collagen Type I and Type III and damage the left ventricular ejection function.Keywords: Activated B cells; Acute myocardial infarction; Collagen; Cytokines; Left ventricular function.