Background/aim: Outer inflammatory protein A (OipA) is an important adhesin of Helicobacter pylori. Our goal was to assess the role of OipA in protection of C57BL/6 mice against H. pylori. Materials and methods: C57BL/6 mice were mucosally immunized with recombinant OipA protein, OipA + propolis, propolis, and phosphate-buffered saline. After vaccination, anti-OipA IgA was measured. Mice were challenged three times with 5 x 107 CFU of the H. pylori B19 strain. Two weeks later, bacterial colonization and inflammation in the stomach was analyzed using standard methods. Results: The CFU number in the OipA group was significantly (P < 0.05) lower than that of the control. The CFU number in the OipA + propolis group was higher than those of the OipA and propolis groups. IgA titers were significantly higher (P < 0.0001) in the OipA group compared to the control and OipA + propolis groups. Propolis did not play an adjuvant effect but it interfered with the efficient vaccine effect of OipA. Conclusion: Results show the effect of vaccination by OipA in protection of the mouse model and the importance of OipA in H. pylori pathogenesis. OipA may be proposed as a suitable oral vaccine candidate against H. pylori infection; however, further study is required to determine adjuvant or adverse effects of propolis toward OipA.