In order to evaluate the oral immunization effect of S2 vaccine for brucellosis in Wuwei City，Gansu Province，and to investigate the antibody changes of mass population immunization，from 2018 to 2021，8 243 sheep blood samples were collected from 71 large-scale farms where sheep was orally immunized with S2 vaccine for brucellosis，to detect immune antibodies by rose bengal plate test（RBPT）and standard-tube agglutination test（SAT）. The results showed that the positive conversion rate was 55.62% 28 days and 16.72% 60 days after oral immunization with S2 vaccine（1×1010 CFU）；for the three years，the positive conversion rate（the rate）was from 53.21% to 57.91% 28 days after immunization，and from15.55% to 17.81% after 60 days，and no significant difference was observed between years（P＞0.05）；the rate was the highest 28 days after vaccination in Tianzhu County and the lowest in Minqin County，with significant difference（0.01＜P＜0.05），but little among other counties/districts（P＞0.05），and no significant difference was observed in the rate 60 days after vaccination among counties/districts（P＞0.05）；the rate was higher in Tibetan sheep（59.04%）and Alpine fine wool sheep（58.06%）28 days after vaccination，and lowest in small fat-tail sheep（51.94%），with significant difference（0.01＜P＜0.05），but little among other varieties（P＞0.05）. 60 days after vaccination，no significant difference was found among different varieties（P＞0.05）；and 28 days after vaccination，the rate was similar（P＞0.05）in the farms with an inventory of less or more than 100 sheep，but extremely different 60 days after vaccination（P＜0.01）. In conclusion，the rate after immunization was relatively low in general，with low duration of antibodies；the immunization effect was basically consistent in different years and counties，and better in Tibetan sheep and Alpine fine wool sheep compared with small fat-tail sheep. It was therefore recommended to improve the immunity of the whole population through developing an appropriate model and dose of vaccine immunization to expand the coverage rate of immunization in consideration of the factors influencing mass immunization.