Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta 1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta 1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta 1 siRNAs reduced the expression of TGF-beta 1 in the livers of CCl4 injection compared with those of control group, and the expression of type I collagen and a-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta 1 siRNAs inhibit TGF-beta 1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human. beta 2006 Elsevier Inc. All rights reserved.