Objective To investigate the effects of original antigenic sin caused by previous expo-sure to influenza A virus subtype H1N1 on the immune response to inactivated H5N1 vaccine. Methods In this study, the BALB/c mice were first infected with A/PR8 (H1N1) virus or immunized with inactivated vaccine to induce immune responses against the A/PR8 virus. Then they were injected once with inactivated H5N1 vaccine at dosages of 0. 01μg, 0. 1μg and 1μg, respectively. The levels of IgG and neutralizing an-tibodies in serum samples were detected after immunization. Four weeks after immunization, the mice were challenged with a lethal dose of H5N1 virus. Some indicators including the survival rate, body weight loss and residue virus titer in lung were recorded for further evaluation. Results The pre-existing anti-A/PR8 antibodies in mice didn′t alleviate the immune responses to inactivated H5N1 vaccine. Conclusion This study indicates that the original antigenic sin associated with the previous exposure to A/PR8 virus has no significant effect on the immune efficacy of H5N1 vaccine.