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Objective: To study the efficacy of linezolid combination with fosfomycin in MRSA catheter-related biofilm infection.Methods: Using an in vitro study to assess alone or combination of linezolid and fosfomycin in planktonic or biofilm, then the fractional inhibitory concentration index, time-kill curve in planktonic and viable bacterial counts in biofilm were calculated.In the biofilm-infected rat model, the synergy efficacy of treatment with linezolid and fosfomycin on infection were studied.Results: The combination of linezolid and fosfomycin showed significant synergistic effects against MRSA in vitro.In the biofilm-infected rat model, as single agent or combination of these two agents not reduced the numbers of white blood cells, but the normal rate of white blood cells in combination agents were higher than single agent.It was a statistical difference that combination agents compared with single agent at viable bacterial counts in biofilm in vivo.Conclusions: Combination of linezolid and fosfomycin not only showed a positive effect in vitro but also improved the therapeutic effect in a biofilm-infected rat model.