Objective ACE2 is a receptor of SARS-CoV. In this paper, the replication of SARS-CoV in murine fibroblasts expressing human ACE2 and ACE2 knockout mice was studied. Methods The murine fibroblasts expressing human ACE2 and ACE2 knockout mice were used to investigate the replication of SARS-CoV and protective effect of ACE2 knockout on SARS infection in mice. Results The SARS-CoV infected and replicated in the murine fibroblast cells expressing human ACE2. The Block of ACE2 expression inhibited the infection and replication of SARS-CoV in vivo. The ACE2 gene knockout showed a protective effect on SARS-CoV infection in mice. Conclusion Our results suggested that ACE2 is a functional receptor for SARS- CoV and a possible target gene for SARS therapy.