Liver cirrhosis is the irreversible end result of chronic liver disease, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors. The ideal strategy for the treatment of liver cirrhosis should include prevention of fibrogenesis, stimulation of hepatocyte mitosis, and reorganization of the liver architecture. We have developed a novel gene therapy approach for rat liver cirrhosis by muscle-directed gene transfer of hepatocyte growth factor(HGF). HGF gene transduction inhibited fibrogenesis and hepatocyte apoptosis, and also produced resolution of fibrosis in the cirrhotic liver. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.