Objective To establish a small animal model of severe acute respiratory syndrome(SARS).Methods We developed a mouse model of human SARS coronavirus infection by introducing the human angiotensin converting enzyme 2(hACE2) gene,serving as the cellular receptor of SARS coronavirus(SARS-CoV),into the mouse genome.The hACE2 gene,driven by the mouse ACE2 promoter,was expressed in the lung,heart,kidney and intestines.The responses of wild-type and transgenic mice to SARS-CoV inoculation were observed.Results At 3 and 7 days after inoculation,SARS-CoV had replication more efficiently in the lungs of transgenic mice.In addition,transgenic mice showed more severe pulmonary lesions,including hyperaemia and haemorrhage in the interstitium,monocyte and lymphocyte infiltration,protein exudation,and alveolar epithelial cell proliferation and desquamation.Other pathological changes,including vasculitis,degeneration and necrosis were found in the extrapulmonary organs in transgenic mice.Viral antigen could be found in the lung and brain.Conclusions Transgenic mice are more susceptible to SARS-CoV infection than wild-type mice and the susceptibility is associated with severe pathological changes resembling human SARS infection.