In order to study the effect of RseB gene deletion on the ability of Vibrio alginolyticus to infect the Lateolabrax maculatus， the LD₅₀， colonization ability and immune response of the L. maculatus after infection were evaluated. The results showed that the LD₅₀ of V. alginolyticus was 2.013×10⁵ cfu/mL， and the LD₅₀ of V. alginolyticus with RseB-deletion was 5.526×10⁵ cfu/mL， and the virulence of RseB-deletion V. alginolyticus decreased by 63.6%. V. alginolyticus mainly colonized in the gill， intestine and skin of L. maculatus. Compared with V. alginolyticus， the degree of intestinal vacuolization and the damage of gill tissue were lower in L. maculatus after challenged with the RseB-deletion V. alginolyticus. Transcriptome sequencing was performed on the head kidney tissues of L. maculatus challenged by wild-type and RseB-deletion V. alginolyticus， respectively. A total of 236 immune-related differentially expressed genes were found， including 122 significantly up-regulated immune genes and 114 significantly down-regulated immune genes. Most of these genes were significantly enriched in specific immune pathways such as Th1 and Th2 cell differentiation， B cell receptor signaling pathway， T cell receptor signaling pathway， and some genes were significantly enriched in apoptosis-related pathways and inflammation-related NF-kappa B signaling pathway. In summary， the results show that RseB-deletion V. alginolyticus can cause immune response of host cells and reduce virulence.