A novel autonomous drug release system based on chemo-mechanical energy was fabricated and tested. The system consists of two integrated units: decompression unit so-called organic engine and drug release unit. Glucose oxidase (GOD) immobilized membrane was utilized to Organic engine for converting chemical energy of the glucose to mechanical work as pressure changes of consumed oxygen in the GOD catalysis. Characteristic of the pressure changes was in good correlation to the glucose concentrations. Afterward, the drug release unit which utilizes the energy of the Organic engine as a power source was fabricated and evaluated by recording its release actions. The system was then fabricated by combining the both units. As a result of the evaluation test, the system showed the feasibility of autonomous glucose control in closed loop feedback setting as a natural pattern of the insulin secretion on feedback of blood sugar levels.