Objective Compare with the immunomodulatory function by Hirsutella sinensis and Paecilomyces hepiali in vivo. Method After the mice were administrated by Hirsutella sinensis and Paecilomyces hepiali.Observed carbon particle clearance function, delayed type hypersensitivity, hemolytic antibody, lymphocyte proliferation and NK cell activity in mice, and Cordyceps sinensis as a positive control. Result 3.0g·kg-1 Hirsutella sinensis and Paecilomyces hepiali can significantly improve the phagocyte index and half of hemolysis value (P<0.01). 3.0g·kg-1 Hirsutella sinensis and Paecilomyces hepiali can significantly improve the T, B lymphocyte proliferation (P<0.01, P<0.05). 3.0g·kg-1 Hirsutella sinensis can significantly enhance the activity of NK cells (P<0.05). 0.5-1.5g·kg-1 Hirsutella sinensis can significantly inhibit the ear edema in mice (P<0.01, P<0.05), at the same time 1.5g·kg-1 Hirsutella sinensis can inhibit the spleen and thymus increases(P<0.01, P<0.05).Conclusion Hirsutella sinensis and Paecilomyces hepiali have Immunomodulatory effects. Hirsutella sinensis.The Hirsutella sinensis were better than Paecilomyces hepiali in immunosuppression and enhance the role of the innate immune system.Paecilomyces hepiali were better than the Hirsutella sinensis in enhanced adaptive immune system. Keyword: Hirsutella sinensis; Paecilomyces hepiali; mice; Immunomodulatory function.