Influenza viruses, featured by high variability, pose a persistent public health threat because of an annual seasonal epidemic in the world and irregular global pandemic, requiring animal models to elucidate their pathogenic mechanisms and advance preventive strategies. Mice have been selected as the primary animal model, although several experimental animals have been used in studies of the influenza virus. However, the limited susceptibility of wild-type influenza viruses to mice poses significant challenges for studying pathogenesis and intervention strategies. Here, to help understand the construction of mouse-adapted influenza viruses, we reviewed the recent research progress in constructing mouse-adapted influenza virus strains to overcome species-specific barriers.