Interferon (IFN) is a kind of cytokines that are included in biodefense and immunological function. IFN is involved in biological defense and immune functions. Our company initiated the development of IFN preparations for companion animals and commercialized the world’s first feline interferon (FeIFN) preparation indicated for feline Calicivirus infection (i.e. the common cold in cats) in 1994. This preparation is commercially available in 45 countries worldwide at present. Furthermore, the canine interferon γ (CaIFN) preparation, Type II IFN preparation for dogs, was approved as a drug for treating atopic dermatitis in dogs. Both products are manufactured in a process using a silkworm-baculovirus expression system, in which silkworms infected with gene recombinant baculovirus express and accumulate the protein in the body fluids. In this chapter, the manufacturing process of animal IFN using the silkworm-baculovirus expression system is introduced.