Advances in medical science and technology inevitably have generated the increasing ramification of disciplines of clinical medicine. Each medical professional tends to be restricted in his/her own specialty, in terms of knowledge, methodology and viewpoint, and often leads to the destruction of the harmonious balance of human body through excessive concentration of a local situation. Human body must be in balance as a complicated system whose behaviors are regulated though huge network of control mechanisms. The medical treatments must be re-considered from this point of view of the totality of human body in face of coming aged society. The integration must be emphasized instead of ramification. The so-called systems medicine is regarded as a methodology of clinical science of the next generation to overcome various bottlenecks of the modern medicine, as well as medical care systems. A core of the system medicine lies in digital technology, particularly modeling and control of human viscera and their protection systems. We propose the notion of model-based medicine as a concrete discipline of system medicine which is based on the well-known internal model control. The methodology of constructing integrative model of human body for model-based medicine is proposed. A preliminary example of model-based medicine for use in ICU(intensive care unit) is shown. As a more realistic example, a new model of glucose-insulin-glucagon dynamics which involves the allostatic effect of neuronal-hormonal regulation is derived, based on which a treatment strategy of model-base medicine is proposed. Some theoretical issues of systems medicine will be discussed.