Macrophages play a crucial role in kidney diseases by exhibiting both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. M1 macrophages contribute to tissue damage, inflammation, and fibrosis, while M2 macrophages aid in tissue repair and regeneration. The NLRP3 inflammasome, present in renal macrophages, is activated by harmful stimuli, leading to the release of pro-inflammatory cytokines (IL-1β and IL-18) and the cleavage of Gasdermin D (GSDMD), which induces pyroptosis and renal dysfunction. The activation of the NLRP3-ASC-caspase-1-IL-1β-IL-18 pathway is a key factor in the pathophysiology of kidney diseases. This review explores the current understanding of macrophage behavior in kidney diseases, emphasizing the role of activated macrophages in both the advancement and recovery phases. It also discusses potential strategies to modulate macrophage polarization and target NLRP3 inflammasomes to facilitate healing in kidney diseases.Macrophages play a crucial role in kidney diseases by exhibiting both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. M1 macrophages contribute to tissue damage, inflammation, and fibrosis, while M2 macrophages aid in tissue repair and regeneration. The NLRP3 inflammasome, present in renal macrophages, is activated by harmful stimuli, leading to the release of pro-inflammatory cytokines (IL-1β and IL-18) and the cleavage of Gasdermin D (GSDMD), which induces pyroptosis and renal dysfunction. The activation of the NLRP3-ASC-caspase-1-IL-1β-IL-18 pathway is a key factor in the pathophysiology of kidney diseases. This review explores the current understanding of macrophage behavior in kidney diseases, emphasizing the role of activated macrophages in both the advancement and recovery phases. It also discusses potential strategies to modulate macrophage polarization and target NLRP3 inflammasomes to facilitate healing in kidney diseases.