Scophthalmus maximus is one of the important species of mariculture in China, and occupies an important position in China's mariculture industry. At present, S. maximus farming industry shows a rapid growth trend, but as S. maximus farming intensification and scale continue to increase, bacterial diseases continue to occur. As pathogens of scabies, Aeromonas salmonicida has caused great economic losses to aquaculture. In order to prepare the inactivated vaccine of A. salmonicida and evaluate its immune effect on S. maximus, HHSM1905 strains were killed by formalin to prepare the inactivated vaccine. The experimental animals were randomly divided into two groups, i.e. immune group and control group. S. maximus was immunized by intraperitoneal injection. The indexes such as serum antibody titer, serum lysozyme activity, acid phosphatase activity and vaccine protection rate were determined. The expression of related immune genes (IL-1β, TLR-5, MHC I, MHC Ⅱ-α and CD4) was studied with β-actin gene as internal reference. The results showed that 2 weeks after vaccination, the antibody titer of immune group was significantly higher than that of control group and reaching the peak value. The lysozyme activity of the immune group reached the peak value 2 weeks after immunization, and remained significantly different from that of the control group at 4 weeks; the acid phosphatase activity of the immune group reached the peak value at 2 weeks after immunization; the relative percentage survival of the combined vaccine was 72.72%. Compared with the control group, IL-1β, TLR-5, MHC I, MHC Ⅱ-α and CD4 immune genes in the immune group had an upward trend, and most of them reached the maximum value at 1-2 weeks, which had significant difference with the control group. In conclusion, the inactivated vaccines of A. salmonicida for S. maximus were successfully prepared in this study. The A. salmonicida inactivated vaccine was effective for preventing A. salmonicida disease, and may provide a novel method for disease prevention in S. maximus culture.