Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in humans. Due to the lack of suitable experimental animal models for HCV infection, the development of more effective treatment of HCV infection and vaccines has been delayed. Chimpanzee is the best experimental animal model for the research of hepatitis C virus (HCV) infection. However, because of its limited in resource, expensive in breeding, and difference in clinical symptoms, thus developing new experimental animal models for HCV-related basic and applied research is imminent. In recent years, as a surrogate animal model, the development of rodent model and other models has been achieved a lot of progress. Using such as genetically modified experimental techniques, those surrogate animals were infected with HCV in vivo and were successfully applied to research in several areas. In this review, we will focus on the achieved progress in naturally infected animal model and transgenic surrogate experimental models, and their advantage and limitation in usage in study on the pathogenetic mechanism of infection, drug evaluation and development of vaccines, and will also discuss the future direction of development of experimental animal models for research of infection with HCV.