Although a variety of gene transfer methods to the liver have been designed, there are some problems such as the transfection efficiency and safety. In the present study, we developed a modified method of gene transfer into the liver by infusion of plasmid DNA via the portal vein followed by electroporation. After green fluorescence protein gene transfer, transgene expressions were detected in 24 h, and then maximally at 3 days, and persisted for 3 weeks. Histological analysis revealed that very mild tissue damage was induced in the liver to which electroporation was applied. In the second study, human hepatocyte growth factor (HGF) was more detected in the liver injected with 500 microg of human HGF gene than 100 microg of human HGF gene. However, serum HGF did not increase with 100 or 500 microg of human HGF gene. Moreover, 500 microg of HGF gene transfer into the liver by using this method could achieve the long survival of all dimethylnitrosamine-treated rats and attenuate the fibrous regions in the liver. These results suggest that HGF gene transfer into the liver via the portal vein using electroporation might be one of the useful methods for the treatment of various liver diseases.