Abstract: Yersinia ruckeri is major pathogenic bacterium that is harmful to the aquaculture of Ictalurus punctatus. The conventional treatment such as antibiotics and chemicals often cause issues in, for example, food safety and drug resistance. The vaccine has been considered to be the most effective method of disease prevention and control. Currently, natural polymer materials have been used as the carrier for fish oral vaccine, and sodium alginate is regarded as an ideal material and has become a hotspot in research. In this study, we prepared the oral microspheres vaccine of Y. ruckeri by using formalin-inactivated Y. ruckeri as the antigen and sodium alginate as the carrier. We also studied the characteristics of this vaccine and evaluated its immune efficacy that was indicated by the serum non-specific immune parameters, the antibody titers and the relative survival rate. We found that the microspheres had a good form with a homogeneous distribution of the particle diameter; the average diameter was(8.761.73) m and the span was 0.47; and the encapsulation efficiency of the vaccine was 94.51%. Moreover, this vaccine exhibited characteristics such as high acid resistance, good enteric solubility, and being safe. The activities of the serum lysozyme, the total superoxide disumutase(T-SOD) and the alternative pathway complement(ACH50) were significantly increased in the vaccinated I. punctatus. The serum agglutination titers reached the peak value of 1:8 in the 5th week, and the specific antibodies were detected in the 8th week after vaccination. The relative survival rate of the I. punctatus was 65.52%. In conclusion, the oral microspheres vaccine of Y. ruckeri effectively protects the fish form the Y. ruckeri disease.