The anamorph of Cordyceps sinensis, Hirsutella sinensis mycelium (HSM), is a material of health food that has been shown to accelerate leukocyte recovery, stimulate lymphocyte proliferation and anti-inflammatory effects. However, the effects of HSM on T lymphocytes activity remain unclear. The aim of this study was to investigate whether HSM has any immune-modulatory effects on cytokine production from T lymphocytes in the murine model. The treated groups were administered HSM powder at a dose of 822 mg/kg body weight for seven weeks. The results indicated that HSM enhance T lymphocytes proliferation, but not B lymphocytes. HSM increased IFNγ production and decreased Th2 cytokines secretion, but not affect regulatory T cells expression. Furthermore, the HSM treatment increased phagocytes and natural killer cells activity. Moreover, HSM also decreased the TNFα production from LPS-stimulated splenocytes. These data suggested that the Hirsutella sinensis mycelium exert immune-regulatory effects on Th cells activity, and enhance innate immunity.