The number of patients with heart failure has increased due to the aging of society. We previously showed that cardiac Ly6C^lo macrophages from aged mice lost the cardioprotective function observed in those from young mice. Notably, our single-cell RNA-sequencing (scRNA-seq) analysis demonstrated that tissue-resident macrophage subpopulations were replaced with aged mice-specific subpopulations. In young mice, cardiac macrophages were constitutively expressed various chemokines, although there was little or no expression of cytokines in the steady state. Our scRNA-seq data revealed lower expression levels of Ccl2, Ccl3, Ccl4 and Cxcl2 and higher expression of CCR5 in aged mice-specific cardiac macrophages. These results suggest that alteration of the expression of chemokines in cardiac macrophages may result in changes in the proportion of each immune cells in the heart of aged mice, triggering age-associated disease induction. We confirm the pathophysiology of macrophage-specific Cxcl2-deficient mice in a transverse aortic constriction (TAC) model to elucidate the regulatory mechanism of progression of tissue fibrosis by macrophage-derived chemokines. Furthermore, we assessed the effects of CCR5 inhibitor on tissue fibrosis in TAC mice. Thus, we clarify the relationship between aging-associated heart failure and phenotypic changes in cardiac macrophages.