Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the corona virus disease 2019 (COVID-19) cases in China and has become a public health emergency of international concern1. Because angiotensin-converting enzyme 2 (ACE2) is the cell entry receptor of SARS-CoV5, we used transgenic mice bearing human ACE2 and infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant macrophages and lymphocytes into the alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, macrophages and alveolar epithelia. The phenomenon was not found in wild-type mice with SARS-CoV-2 infection. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. The mouse model with SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutics and vaccines as well as understanding the pathogenesis of COVID-19.