Abstract:[Objective] To establish a zebrafish model of Edwardsiella tarda infection for the pathological studies and the development of drugs. [Methods] Zebrafish were artificially infected through different routes to simulate natural infection states, and the pathogenic mechanism of E. tarda in zebrafish was studied based on mortality, behavioral changes, biochemical indicators, and changes in the antioxidant capacity. [Results] Among the three infection routes, intraperitoneal injection showed the strongest pathogenicity. The zebrafish infected with E. tarda presented symptoms such as exophthalmos, anal bleeding, surface ulcers, and ascites. Pathological examination showed that the infected zebrafish developed acute inflammation, with extensive necrosis, degeneration, and shedding of hepatocytes and phagocytes gathering around. The TX strain was isolated from the diseased zebrafish and identified as E. tarda by polymerase chain reaction (PCR) with specific primers. The median lethal dose (LD50) of the strain was determined to be 3.65×102 colony forming units (CFU)/individual. Compared with the control group, the infection model established by injection showed a decrease of 22.26% in superoxide dismutase activity and increases of 16 folds in malondialdehyde content, 38.99% in acid phosphatase activity, and 24.36% in alkaline phosphatase activity. [Conclusion] An E. tarda infection model was established by intraperitoneal injection in zebrafish, which exhibited typical disease symptoms and physiological and biochemical characteristics, and the LD50 was determined. The findings provide a theoretical reference for the pathological studies and the drug development for E. tarda infections in aquatic animals.