We obtained a strain of oxytetracycline-resistant Edwardsiella tarda named LTB4-ROTC through artificial passaging in the TSB medium，the minimum inhibitory concentration (MIC) of LTB4-ROTC was 12.5 μg/mL, which was 32 folds increase contrast to LTB4-S strain. Proteomic analysis was conducted to profile the different protein expression.