Objective To establish a mouse model of methicillin-resistant Staphylococcus aureus(MRSA) systemic infection with a MRSA strain isolated from clinical samples. Methods Forty-four ICR mice were randomly divided into experimental group (28 mice) and control group (16 mice). The mice were infected with MRSA (1×10⁷ CFU/mL) by tail vein injection after the mice were treated with cyclophosphamide (100 mg/kg) i.p. for immunosuppression. Survival analysis, peripheral blood white blood cell count, tissue bacterial loads and pathological examination were used to evaluate the models. Results At 2 days after MRSA infection, the treated mice began to die and the cumulative mortality rate reached to 60% at 14 days post-infection. The peripheral blood leukocyte count was significantly increased. MRSA test was positive in the kidneys, joints, lung, liver and brain. The bacterial loads in kidneys reached to 10⁹ CFU/g in joints, lung, liver and brain reached to 10⁴ to 10⁹ CFU/g. Histopathological changes of multiple organ infection were observed in the kidney, heart, lung, liver, brain and joint tissues. Conclusions We have successfully established a mouse model of MRSA systemic infections. It can be a useful model for the study on pathogenesis and new drug development and so on of MRSA infection.