Current understanding of various biology including immunology has largely come from the mouse studies. However, it is becoming increasingly apparent that several aspects of human immune system are different from those in the mouse, making clinical translation of the knowledge gained from mouse research difficult. In order to understand normal and diseased human immunity, direct in vivo examination of human immune system is required. To this end,we have developed humanized mice reconstituted human immunity in mice. Humanized mouse system enables us to investigate differentiation, mobilization, and function of human immunity in thymus, spleen, and LNs. In addition to the understanding of normal human immunity, we are currently developing various models of human diseases such as leukemia, infectious diseases, and primary immuno-deficiencies. We aim to overcome intractable human diseases through understanding of the in vivo pathophysiology of these diseases.