Objective To establish and analyze a mouse model of Staphylococcus aureus-induced arthritis (Staphylococcus aureus septic arthritis, SA), and provide an animal model for arthritis mechanism research and drug development. Methods Mice were immunosuppressed with cyclophosphamide, then intravenously inoculated with Staphylococcus aureus. The gross characteristics of the joints were observed, the arthritis indexes were analyzed, and the pathological scores of the model mice were evaluated. Results From the first day after bacterial inoculation, the mouse joints were swollen. Pathological examination revealed lesions varying from mild and disarranged joint synovial hyperplasia to synovial thickening and intra-articular invasion, and increased neutrophil infiltration. Conclusions A mouse model of Staphylococcus aureus-induced arthritis is successfully established in this study. This model can be developed in a relatively short time, can not only simulate the clinical symptoms and signs and disease progression of human arthritis, but also to a certain extent reflects the etiology, infection and immunological mechanisms of human arthritis.