In the present study, the immunomodulatory effect of Neem (Azadirachtaindica)seed aqueous, ethanolic extracts and Candida albicans cell wall mannoproteins on theimmune response of mice vaccinated with Brucella Rev-1 vaccine was investigated. Thestudy was conducted on two main groups(160 mice for each group), Each group wasdivided into eight subgroups 20 mice for each (I: treated with distilled water, II: treatedwith the Brucella Rev-1 vaccine, III: treated with mannoproteins, IV: treated with neemaqueous extract, V: treated with neemethanolic extract, VI, VII and VIII: treated withmannoproteins, neem aqueous extract and neemethanolic extract, respectively, then theywere vaccinated with Brucella Rev-1). All these treatments were carried out on day 1and then vaccinated with brucella Rev-1 vaccine on day 4 .Then the mice were tested asfollows , on day 8 after vaccination(serum IFN-γ level), day 21 for (anti-Brucellaantibody titer). The doses of both plant extracts and mannoproteins represented 10% ofthe calculated LD50 (neem extracts: 3.8096 g/Kg mannoproteins: 5.7144 mg/Kg), whichwere given subcutaneously. Mice of the second main group were injected with theimmune suppressive drug prednisolone (5mg/Kg) 5 days prior to the treatments, whichcarried out on mice of the first main group. The results demonstrated clearimmunomodulatory effects (improvement of non-specific, humoral immunity) of thetested immunomodulators in mice vaccinated with Brucella Rev-1 as compared withmice that were not treated with Neem extracts or mannoproteins. In this regard, Theinterferon-γ showed a significant increase (P≤ 0.01) serum level in immunomodulatortreatedand -vaccinated mice in comparison with negative and positive groups, and againgroup VII showed the highest increase. The anti-Brucella antibodies assessed by indirectImmunoflourescent test also showed a significant increase titer in immunomodulatortreatedand -vaccinated mice in comparison with negative and positive groups .Conclusion: The aqueous and ethanolicNeem seed extract reported the highestenhancement in all immunological parameters employed in comparison withmannoproteins of Candida albicans cell wall.