Skeletal muscle is a promising target tissue for the gene therapy of both muscle and non-muscle disorders. Gene transfer into muscle tissue can produce a variety of physiologically active proteins and may ultimately be applied to treatment of many diseases. A variety of methods have been studied to transfer genes into skeletal muscle, including viral and non-viral vectors. Recently, we have developed the polyethyleneglycol (PEG)-modified liposomes entrapping echo-contrast gas known as ultrasound (US) imaging gas. We have called the liposomes "Bubble liposomes" (BLs). We have further demonstrated that US-mediated eruption of BLs loaded with naked plasmid-DNA is a feasible and efficient technique for gene delivery. In this study, to assess the feasibility and the effectiveness of BLs for the gene therapy of disorders, we tried to deliver therapeutic genes (anti-inflammatory cytokine; IL-10 or anti-angiogenic factor; hK1-5) into skeletal muscles of arthritis or tumor model mice by the gene delivery system with BLs and US exposure. As a result, their disease symptom was efficiently improved by the systemic secretion of therapeutic proteins. Thus, this US-mediated BLs technique for muscle gene transfer may provide an effective noninvasive method for arthritis or cancer gene therapy in clinical use. In addition, it may be applicable for the gene therapy of other non-muscle and muscle disorders.