The liver is an organ with vital functions and dysfunctions of the liver are potentially fatal. Although, the liver is known to be highly regenerative organ, it is still difficult to induce regeneration in dysfunctional liver to treat diseases. To overcome liver disease, it is essential to gain insights into genetic and cellular mechanism underlying liver disease and regeneration. To this end, it is prerequisite to develop animal models for human liver disease and regeneration. Medaka is a new animal model with two unique features. Firstly, we can find liver disease models by randomly destroying their genes. We have found 29 candidates for liver disease using Medaka fish. Secondly, since the body of Medaka embryos are transparent, we can observe cell behavior in the liver in living Medaka fish. Taking advantage of this, we have developed a special technique to discover what kind cell behavior underlies liver diseases and regeneration. We will combine these disease models and the special technique to discover what kind of cellular and genetic mechanisms underlie liver disease and regeneration. Our findings will be useful for generating therapeutic means to cure human liver disease.