Abstract: Major histocompatibility complex (MHC) is widespread in vertebrates, and is a gene cluster which encoding immune and immune-related protein receptor. In fish, because of its high polymorphism, it is so favored to the genetic, evolutionary and breeding for disease resistance and so on. The molecular structure and function, cloning and tissue distribution of the MHC II genes, and the relationship between genetic characteristics and disease resistance gene polymorphism were summarized in this paper; and research priorities in fish MHC II in the future were discussed.