Hepatocyte growth factor (HGF) has been reported to be a renal regeneration factor. We previously reported that HGF acts as a renotropic factor, inducing cell recovery from ischemic injury or drug toxicity. Gene transfer by electroporation, which uses plasmid DNA as the vector, has several advantages over the conventional gene transfer method using viral vectors, inducing the ability to perform repeated transfers without apparent immunologic responses to the DNA vector. We recently demonstrated that electroporation of the HGF gene into skeletal muscle was an effective treatment for liver injury in an animal model. We presently investigated prevention of development of chronic renal disease by repetitive HGF gene transfer in rats with 5/6 nephrectomy. Hepatocyte growth factor gene transfer-treated rats showed better growth in body weight than untreated rats. Histologic changes such as glomerulosclerosis and interstitial fibrosis were significantly ameliorated by HGF gene transfer compared with untreated rats. Hepatocyte growth factor gene transfer by electroporation into skeletal muscle is feasible and effective against morphologic injury in subtotally nephrectomized rats.