Liver fibrosis is characterized by excessive extracellular matrix accumulation during chronic liver disease progression. Hepatic stellate cell (HSC) activation involves metabolic reprogramming, while both HMGB1 and β-catenin pathways have been implicated in HSC activation and liver fibrosis progression. Given irisin's established role in metabolic regulation and emerging evidence of its anti-fibrotic properties, we investigated its effects on HSC activation and liver fibrosis, focusing on potential metabolic regulation through the HMGB1/β-catenin pathway. Using both in vitro HSC-T6 cell culture and in vivo CCl