The present study was conducted to evaluate the immunomodulatory effects of Dangguijakyak-san(당귀작약산). We investigated the effects of cell proliferation in mouse spleen cell and RAW 264.7 macrophages cells. Dangguijakyak-san enhanced mitogenic activity in the dose-response manner in mouse spleen cells and RAW 264.7 macrophages cells. In nitric oxide (NO) synthesis and iNOS mRNA expression by Dangguijakyak-san, Dangguijakyaksan alone had an effect on NO synthesis and iNOS mRNA expression in RAW 264.7 cells. NO production and iNOS mRNA expression which is excessively induced by LPS decreased after treatment of Dangguijakyak-san. The expressions of cytokine gene by Dangguijakyak-san investigated using reverse transcription polymerase chain reaction (RT-PCR). In RT-PCR, IL-1α, IL-1β and IL-6 mRNA expressions induced in Dangguijakyak-san-treated RAW 264.7 cells. These data indicate that 1) Dangguijakyak-san can modulate various immune response and 2) the immunomodulatory effects of Dangguijakyak-san may be, in part, associated with the regulation of NO synthesis, the expressions of these cytokine as well as the mitogenic effect on spleen cells and macrophages cells.