Abstract: To study the immune response of mandarin fish (Siniperca chuatsi) to attenuated Flavobacterium johnsoniae strain M170, we used fluorescence quantitative RT-PCR method for determination of liver lysozyme (Lys) gene in spleen, gene expression dynamics of immunoglobulin (IgM), and detected the changes of the Lys activity and the antibody titer in serum. The results show that after the F.johnsoniae attenuated accine immunization, the Lys gene expression in liver increased significantly (P < 0.05), reaching the peak at the 48^th hour, 10.9 times higher than that of the control group (P < 0.05), and had been higher than the control group significantly until the 28^th day (P < 0.05). Meanwhile, the Lys activity in serum increased significantly, reaching the peak on the 2^nd day, 4.35 times higher than that of the control group (P < 0.05) and was equivalent to the level of the control group on the 6^th day. The relative expression of IgM gene from mandarin fish spleen began to increase and had been significantly higher than that of the control group since the 7^th day (P < 0.05), 98.7 times higher than that of the control group until the 28^th day (P < 0.05). The antibody titer in the immune fish serum was higher than that of the control group significantly since the 7^th day (P < 0.05), reaching the peak (2⁶) on the 28^th day. On the 28^th day after immunization, the strain M168 was used to attack the virus, and the relative survival rate of the immunized group was higher than that of the control group significantly, and the relative percentage survival (RPS) was 85.9%. The results show that the specific and non-specific immune response can be induced by attenued F.johnsoniae M170 and provide good protection for mandarin fish.