Objective To establish a mouse model of pneumonia with C57BL/6 and MyD88KO mice after infection with an isolated ST23 Klebsiella pneumonia (KP) strain, which was an epidemic strain and identified by multilocus sequence typing (MLST). Methods Fifty C57BL/6 mice were randomly di-vided into three groups:KP infection,control and immunosuppressive groups. Thirty MyD88KO mice were divided into KP infection and control groups. All mice in the KP infection groups were infected with 50 μl of ST23 KP strain through nasal dripping. Equal volume of PBS was used to set up the control groups. Mice in the immunosuppressive group were first injected with cyclophosphamide for three days and then infected with equal volume of ST23 KP strains through nasal dripping. Clinical signs and survival curves during KP infec-tion were monitored. Moreover,pulmonary bacterial loads and histopathological changes in the KP-infected mice were detected at different time points. Results ST23 KP-infected C57BL/6 mice showed inflammatory cell infiltration in lung tissues on the 10th day and remained alive on the 21st day. All ST23 KP-infected MyD88KO mice died on the 5th day with severe histopathological damage in lung tissues. C57BL/6 mice that pretreated with cyclophosphamide had similar symptoms with MyD88KO mice after infection and died on the 5th day. Some critical inflammatory mediators such as TNF-a,nitric oxide synthase 1 (NOS1) and NF-κBp65 were up-regulated in lung tissues of mice after KP infection. No inflammatory syndromes were found in the mice of PBS control groups. Conclusion This study suggests that the mouse model of pneumonia is successfully established with KP strain. It will help researchers to study the characteristics and pathogenesis of ST23 KP strain-induced pneumonia and to seek safe treatments in the future.