Gamma irradiation (γIR) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of γIR while the effect of low dose of γIR on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of γIR on murine spleen cells. It was evaluated if γIR affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-γ, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-κB medicated mechanism. Exposure of 137 Cs-γIR below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-IκBα were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of γIR less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.