Our previous study indicated that the antibody against the major antigenic site of SE Fli C (g.m. region) is characteristically produced after the application of SE bacterin, however, the antibody is not produced in chickens after SE infection. In the present study, we determined histologically if the major antigenic site could be a candidate antigen for SE subunit vaccine. When Layermune SE, a commercial SE bacterin, was injected subcutaneously into the shoulder region as a positive control, the following histological changes were observed: formation of epithelioid granuloma with epithelioid cells and multinuclear giant cells surrounding necrotic sites and oil cysts (Indicator 1); a perivascular accumulation of lymphocytes near the granulation tissue (Indicator 2); peripheral fibroplasia encapsulating the granulation tissue (Indicator 3). On the other hand, at the injection site from the incomplete Freund adjuvant as a negative control antigen, there was only hyperplasia of the connective tissues around oil cysts. By using these indicators, the histological changes induced by injection of major antigenic site (SEp9) of Fli C, Fli C, and SE somatic antigen were evaluated. Histological changes after the injection with SEp9 demonstrated Indicators 2 and 3. The injection with SE Fli C demonstrated all three indicators. Contrarily, de-flagellated SE antigen injection induced only Indicator 3. The present results suggest that the antigen g.m. site of SE Fli C (SEp9) may play an important role as a subunit vaccine not only for including continuous immunological reaction in SE infection in chickens but also for antigen presentation.