An ideal animal model for hepatitis E virus (HEV) research is still unavailable. To assess the possibility of using Mongolian gerbils as animal model, 28 gerbils were randomly assigned into two groups, 14 for each group. Gerbils in Group 1 were inoculated with a genotype 4 HEV recovered from swine via the intraperitoneal route. Group 2 was used as a negative control and inoculated with normal suspension of swine liver. Sera and feces samples were collected once a week for 7 weeks. Two gerbils from both groups were necropsied weekly, pathological changes were recorded and tissue samples collected for further investigation. Distribution of the virus antigens was determined by immunohistochemical staining. Nested RT-PCR and a commercial ELISA kit were used to confirm the infection. Research results demonstrated that Mongolian gerbils in Group 1 were successfully infected with HEV. Viremia and fecal virus shedding lasted nearly 4 weeks, while the virus could be detected constantly in the liver, and occasionally in the kidneys and spleen as well as the small intestine. Histopathological changes in the liver were present with slight, multifocal, lymphohistiocytic infiltrates in the portal tracts or distributed irregularly throughout the liver. HEV antigens could be detected in the liver and intestine, and were mainly distributed in the nuclei. The results indicate that Mongolian gerbils could be used as an ideal animal model for the study of HEV.