Desired for establishment of the prevention and control method of tilapia streptococcal disease, surface immunogenic protein (SIP) gene of Streptococcus agalaciate was prokaryotically expressed, and SIP fusion protein was used as core-material and natural polysaccharideⅡ as shell material. The oral polyacrylic resin microencapsulated vaccine of S. agalaciate was prepared. The average diameter of microencapsulated vaccine particles was 826.5 μm, the package rate was 72.02% and the amount of medicine loaded was 6.11%. Solubility of protein SIP oral microencapsulated vaccine in five pH conditions was pH 6.80>pH 7.20>pH 9.18>pH 4.68>pH 2.00. The in vitro experiment showed that oral microencapsulated vaccine releases protein SIP 5426.0 μg in simulated intestinal fluid, however, only 395.5 μg in simulated gastric fluid, and accumulative release rate was 90.51% in simulated intestinal fluid of 240 min. The vaccine could avoid destroying gastric acid and had good characteristics of intestines dissolution. Tilapias (Oreochromis niloticus) were immunized by oral microencapsulated vaccine. The antigens (SIP proteins) were respectively used at 5 μg and 10 μg antigens per gram of tilapia each time of immunization. After every immunization, a high level of IgM specific to SIP was detected with the antisera from the tilapia, the titer of 5 μg group was 100^-1~400^-1, and the titer of 10 μg group was 200^-1~1600^-1. The results indicated the fish had produced high titer antibody against S. agalaciate. After four times of immunization, tilapias were challenged by artificial infection with S. agalactiae and relative percent survivals (RPS) were calculated. The RPS of 5 μg group and 10 μg group were 44.45% and 66.67% respectively. The results showed that the oral microencapsulated vaccine was a convenient, safe and effective method for immune control of S. agalactiae in tilapia.