Abstract: To establish an enteritis model in largemouth bass (Micropterus salmoides), this study used dextran sulfate sodium (DSS) as the inducing agent. The extent of intestinal damage and the disease activity index (DAI) after induction were evaluated to identify the optimal dose and administration route. On this basis, changes in water quality, intestinal inflammation, structural regulation-related gene expression, reactive oxygen species (ROS) content, and intestinal morphology were examined at different time points after induction. The results showed that oral gavage with 5.0% DSS was the optimal induction method and dose. On day 1 after induction, the concentrations of protein, ammonia nitrogen, and H2S in the culture water increased significantly (P<0.05); the expression levels of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were the highest, all exceeding 32-fold higher than those of the control group (P<0.05); and ROS content and myeloperoxidase (MPO) activity also reached their highest levels (P<0.05). On day 3 after induction, the expression levels of the anti-inflammatory factors TGF-β1 and IL-10 were the highest, at 38- and 82-fold those of the control group, respectively (P<0.01); the expression levels of the tight junction-related genes ZO-1, CLDN-1, and OCLN were the lowest, at 2%, 4%, and 3% of those in the control group, respectively (P<0.05); and intestinal structural damage was most severe. By day 5 after induction, the inflammatory response had gradually subsided and returned to control levels by day 7. These findings provide a reference method and evaluation index system for studying enteritis in largemouth bass and also offer an important methodological and scientific basis for enteritis research in other cultured fish species.