© 2018, Japan Society of Drug Delivery System. All rights reserved. For therapy of digestive diseases, generally drug treatment has been employed. There have been problems due to even drug distribution in the target and non-target organ. Since it is difficult to attain local drug activity after conventional administration such as intravenous and oral routes, we have tried to develop a new administration system utilizing drug absorption from the organ surface such as liver in the peritoneal cavity. As a non-invasive procedure, endoscopic surgery would enable us to achieve drug targeting to the diseased region in the peritoneal cavity. Although direct drug application to the organ surface could yield local drug availability, drug absorption characteristics from the organ surface such as liver surface had not been reported in the literature. Therefore, we first analyzed the efficiency of absorption of several organic anions and dextrans of various molecular weights, as marker compounds, following application to the rat liver surface in vivo employing a cylindrical diffusion cell. Each compound was absorbed from the rat liver surface with the different rates depending on the physicochemical properties. The absorption process from the liver surface might not obey an active transport system because of no detectable effect by dose and transport inhibitors. In addition, molecular weight and lipophilicity were found to be one of determinant factors of absorption through the liver surface. The ability of targeting to the desired region in the liver was enhanced significantly by application to the liver surface, compared to intravenous administration. Viscous additives, absorption enhancer, and vasomodulaters were proved to be effective to improve the drug availability in the target region. We also have obtained several expecting results from the application of this new drug delivery system for anticancer drugs. On the other hand, I have clarified the characteristics of drug absorption from the surfaces of the kidney, stomach, cecum and small intestine, and expect to apply the physiological findings to other fields. Furthermore, it is possible to apply the organ surface administration to genetic medicine. We successfully enhanced transgene expression onto the organ surface based on various strategies.