Macrophages are crucial mediators in the development of inflammatory diseases, including kidney diseases. Unresolved renal inflammation can progressively develop into chronic kidney disease (CKD), resulting in structural and functional impairment of the injured kidney due to renal fibrosis and leading to irreversible end-stage renal disease (ESRD). Increasing evidence suggests that phenotypic changes in macrophages are essential for CKD development and progression. Interestingly, advanced bioinformatics and single-cell RNA-sequencing analyses have revealed the crucial mechanism of macrophage-myofibroblast transition, which may be a novel therapeutic target for renal fibrosis. Therefore, a better understanding of the immunodynamics of macrophages in diseased kidneys may help identify effective therapeutic strategies for unmet clinical needs. This review summarizes the regulatory roles and underlying mechanisms of macrophages in renal fibrosis and their therapeutic implications in kidney diseases, including ESRD.