Liver fibrosis is a chronic wound-healing response of the liver, essentially characterized by diffuse excessive deposition and abnormal distribution of the extracellular matrix (ECM). Although etiological therapy can slow fibrosis progression, drug development directly targeting the fibrotic process still faces substantial challenges, and clinical options remain extremely limited. Traditional Chinese medicine (TCM) has attracted extensive attention in the field of liver fibrosis research due to its multi-component, multi-target, and multi-pathway properties. However, current studies are still predominantly based on preclinical experiments, and systematic integration of mechanisms and sorting of clinical evidence are still inadequate. This review outlines the pathogenesis of liver fibrosis, with emphasis on the polarization of Kupffer cells, the capillarization of liver sinusoidal endothelial cells, the activation of hepatic stellate cells, and ECM metabolic imbalance. Antifibrotic effects of active components from herbs are summarized by chemical categories. Furthermore, the interactive network of signaling pathways is integrated from three hierarchical levels—the “inflammation initiation, metabolic regulation, and fibrotic progression”—to explore the systemic mechanisms underlying synergistic modulation by multiple components of TCM. Finally, the limitations of current research are identified, and future directions driven by cutting-edge technologies, including multi-omics integration, single-cell sequencing, artificial intelligence-based screening, and etiology-stratified precision therapy, are discussed. This review provides insights into mechanism interpretation and clinical translation of TCM against liver fibrosis.

traditional Chinese medicine  /  liver fibrosis  /  Kupffer cells  /  hepatic stellate cells  /  extracellular matrix