Aim Plasma apolipoprotein AI (apo AI) play an important role in reverse cholesterol transport and have becoming attractive target for prevention or treatment of atherosclerosis. The present study was undertaken to search for the possibility of human apo AI gene expression and secretion to blood by transferred Ad-RSV-apo AI into mouse skeletal muscles and developing mathod of atherosclerotic gene therapy. Methods An E1-/E3- adenoviral vector, with an RSV-driven human apo AI cDNA expression vector (Ad-RSV-apo AI) was constracted. Transfected myogenic cells in vitro or directly injected into mouse skeletal muscle with the vector. The result was examined by ELISA and immuncytochemistry. Results In the primary cultured myoblasts, the expression level of apo AI in the culture medium increased with the increassing MOI of Ad-RSV-apo AI (from 10 5 pfu to 10 8 pfu). The expression of apo AI was also increased with time. It peaked on the 6th day .After direct injection of Ad-RSV-apo AI into muscle, apo AI mass could be detected, which peaked on day 5 both in the muscle and plasma. On day 30, apo AI was disappeared in the plasma, but the expression in the muscle existed till day 40. Conclusions Apo AI gene can be expressed in the skeletal muscle and secreted to the circulation. It might be an approach for the atherosclerotic gene therapy.