Hepatitis E virus (HEV) is a zoonotic pathogen and all four established genotypes of HEV belong to asingle serotype. The recently identified rabbit HEV is antigenically and genetically related to humanHEV. It is unclear whether rabbit HEV belongs to the same serotype as human HEV. The purpose ofthis study was to determine the serotypic relationship between rabbit and human HEVs. HEV ORF2recombinant capsid protein p166 (amino acids 452–617) of four known HEV genotypes and rabbit HEVwere used to induce immune serum, which were evaluated for their ability to neutralize human HEVgenotype 1, 4, and rabbit HEV strains by an in vitro PCR-based HEV neutralization assay. Immune seraof five kinds of p166 proteins were all found to neutralize or cross-neutralize the three different HEVstrains, suggesting a common neutralization epitope(s) existing between human and rabbit HEV. Rabbitmodels of a second-passage rabbit HEV strain, JS204-2, and a genotype 4 human HEV strain, NJ703, wereestablished as evidenced by fecal virus shedding, viremia and anti-HEV IgG seroconversion. Six rabbits,recovered from JS204 infection, were challenged with NJ703, and another six recovered from NJ703infection were challenged with JS204-2. After challenge, viremia was not detected, shorter fecal virusshedding durations and obvious early stage declines in anti-HEV IgG values were observed. The resultsfrom this study indicate that rabbit HEV belongs to the same serotype as human HEV.