Macrophages are key regulators of fibrosis, playing a central role in both its initiation and resolution. They interact closely with collagen-producing myofibroblasts and produce profibrotic mediators such as TGF-β1 and PDGF, which activate fibroblasts and promote ECM deposition. Macrophages also regulate fibrosis by secreting chemokines that recruit inflammatory cells and by phagocytosing dead cells, which can either promote or resolve fibrosis depending on the type of cell being removed. Macrophages can also regulate fibrosis by controlling ECM turnover through matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). In liver fibrosis, macrophages are a major source of TGF-β1 and PDGF, which contribute to fibrogenesis. They also play a role in the resolution of fibrosis by phagocytosing apoptotic myofibroblasts and reducing the production of profibrotic factors. Additionally, macrophages can produce and activate TGF-β1, which can either promote or inhibit fibrosis depending on the cell type and context. Th2 cytokines such as IL-4 and IL-13, which are produced by alternatively activated macrophages (AAMφ), also contribute to fibrosis by stimulating collagen synthesis and promoting myofibroblast activation. AAMφ are characterized by the expression of Arg-1 and are involved in both pro- and antifibrotic processes. They can suppress Th2 responses and reduce fibrosis by depleting arginine, an essential amino acid for fibroblast proliferation. However, in some cases, AAMφ can exacerbate fibrosis by promoting Th2 responses. The role of macrophages in fibrosis is complex, with different subpopulations playing distinct roles in various stages of the fibrotic process. Macrophages also regulate fibrosis by secreting factors such as chitinases and chitolectins, which are involved in Th2-type immune responses. Additionally, macrophages contribute to the resolution of fibrosis by producing MMPs that degrade the ECM and by phagocytosing cellular debris. The heterogeneity and plasticity of macrophages make them a key target for therapeutic interventions in fibrotic diseases. Understanding the specific roles of different macrophage subpopulations in fibrosis is crucial for developing effective treatments.Macrophages are key regulators of fibrosis, playing a central role in both its initiation and resolution. They interact closely with collagen-producing myofibroblasts and produce profibrotic mediators such as TGF-β1 and PDGF, which activate fibroblasts and promote ECM deposition. Macrophages also regulate fibrosis by secreting chemokines that recruit inflammatory cells and by phagocytosing dead cells, which can either promote or resolve fibrosis depending on the type of cell being removed. Macrophages can also regulate fibrosis by controlling ECM turnover through matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs). In liver fibrosis, macrophages are a major source of TGF-β1 and PDGF, which contribute to fibrogenesis. They also play a role in the resolution of fibrosis by phagocytosing apoptotic myofibroblasts and reducing the production of profibrotic factors. Additionally, macrophages can produce and activate TGF-β1, which can either promote or inhibit fibrosis depending on the cell type and context. Th2 cytokines such as IL-4 and IL-13, which are produced by alternatively activated macrophages (AAMφ), also contribute to fibrosis by stimulating collagen synthesis and promoting myofibroblast activation. AAMφ are characterized by the expression of Arg-1 and are involved in both pro- and antifibrotic processes. They can suppress Th2 responses and reduce fibrosis by depleting arginine, an essential amino acid for fibroblast proliferation. However, in some cases, AAMφ can exacerbate fibrosis by promoting Th2 responses. The role of macrophages in fibrosis is complex, with different subpopulations playing distinct roles in various stages of the fibrotic process. Macrophages also regulate fibrosis by secreting factors such as chitinases and chitolectins, which are involved in Th2-type immune responses. Additionally, macrophages contribute to the resolution of fibrosis by producing MMPs that degrade the ECM and by phagocytosing cellular debris. The heterogeneity and plasticity of macrophages make them a key target for therapeutic interventions in fibrotic diseases. Understanding the specific roles of different macrophage subpopulations in fibrosis is crucial for developing effective treatments.