Fibrosis is a chronic inflammatory condition characterized by excessive deposition of extracellular matrix components, particularly collagen, leading to tissue scarring. It results from persistent inflammatory responses to various stimuli, including infections, autoimmune reactions, and tissue injury. Myofibroblasts, the primary cells responsible for collagen production, are derived from multiple sources, including resident mesenchymal cells, epithelial cells, and circulating fibrocytes. These cells are activated by various signals, including cytokines, chemokines, and pathogen-associated molecular patterns. Fibrosis is driven by distinct mechanisms from those regulating inflammation, with ongoing inflammation sometimes necessary for fibrosis progression. Key regulators include TGF-β, IL-13, and other cytokines, as well as chemokines like CCL2 and CCL3, which recruit myofibroblasts and macrophages to sites of injury. Th1 and Th2 cells differentially regulate fibrosis, with Th2 responses being more closely associated with fibrotic processes. IL-4, IL-5, IL-13, and IL-21 play significant roles in fibrosis, while TGF-β is a major driver of fibrosis through its effects on collagen production and ECM remodeling. Angiotensin II also contributes to fibrosis by promoting TGF-β signaling. Regulatory mechanisms, such as IL-10 and the IL-13 decoy receptor, can suppress fibrosis. While fibrosis is often considered irreversible, recent evidence suggests that it may be reversible in some cases. Antifibrotic therapies targeting cytokines, chemokines, and MMPs are being explored, with the goal of restoring tissue function and preventing fibrosis progression. The development of effective antifibrotic drugs remains a critical challenge in treating chronic fibrotic diseases.Fibrosis is a chronic inflammatory condition characterized by excessive deposition of extracellular matrix components, particularly collagen, leading to tissue scarring. It results from persistent inflammatory responses to various stimuli, including infections, autoimmune reactions, and tissue injury. Myofibroblasts, the primary cells responsible for collagen production, are derived from multiple sources, including resident mesenchymal cells, epithelial cells, and circulating fibrocytes. These cells are activated by various signals, including cytokines, chemokines, and pathogen-associated molecular patterns. Fibrosis is driven by distinct mechanisms from those regulating inflammation, with ongoing inflammation sometimes necessary for fibrosis progression. Key regulators include TGF-β, IL-13, and other cytokines, as well as chemokines like CCL2 and CCL3, which recruit myofibroblasts and macrophages to sites of injury. Th1 and Th2 cells differentially regulate fibrosis, with Th2 responses being more closely associated with fibrotic processes. IL-4, IL-5, IL-13, and IL-21 play significant roles in fibrosis, while TGF-β is a major driver of fibrosis through its effects on collagen production and ECM remodeling. Angiotensin II also contributes to fibrosis by promoting TGF-β signaling. Regulatory mechanisms, such as IL-10 and the IL-13 decoy receptor, can suppress fibrosis. While fibrosis is often considered irreversible, recent evidence suggests that it may be reversible in some cases. Antifibrotic therapies targeting cytokines, chemokines, and MMPs are being explored, with the goal of restoring tissue function and preventing fibrosis progression. The development of effective antifibrotic drugs remains a critical challenge in treating chronic fibrotic diseases.