Objective To establish a SKH-1 hairless mouse model of skin and lung infection by methicillin-resistant Staphylococcus aureus(MRSA) aerosol and its evaluation system. Methods 48 SKH-1 hairless mice were randomly divided into PBS control group, infection group and infection with scald group. After the dorsal skin of the infection with scald group were thermally injured, mice were challenged with aerosolized MRSA(ST-239) through the respiratory tract, then the models were evaluated by body weight, blood tests, bacteraemia rate, skin and organs infection measuring, histopathological observations and multi-PCR for the nuc and mecA genes detection. Results Compared with the other two groups, the infection with scald group had evident weight loss, remarkable increase of WBC count and a bacteraemia rate of 100%. The number of viable S. aureus in the skin and lungs was 108CFU/g and 106CFU/g respectively, inflammatory lesions of the infected tissues were obvious under the light microscope. The results of immunohistochemistry showed that CD138 expressed positively in the skin, and positive results were also found with both nuc and mecA genes in the infected tissues of the infection with scald group. Conclusion We established a scald SKH-1 hairless mouse model, challenged with aerosolized MRSA, which can well simulate clinical burn patients with secondary infection of MRSA pneumonia. This mouse model is of important clinical application value for the evaluation of MRSA-related antimicrobial treatments.