Abstract: Background: Ginseng, the root of Panax ginseng, has been extensively used in traditional oriental medicine and is a modern pharmaceutical reagent for the prevention of various human diseases, including cancer. Ginsenosides are the major active component of ginseng and exhibit immunomodulatory effects. However, the mechanism and function underlying such effects have not been fully elucidated, especially in human monocytes and dendritic cells (DCs).Methods: We investigated the immunomodulatory effect of ginsenosides from the root of Panax ginseng on CD14+ monocytes purified from human adult peripheral blood mononuclear cells (PBMC) and differentiation into DCs that affect CD4+ T cell activity.Results: The results showed that tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 increased in monocytes upon treatment with ginsenoside fractions through phosphorylation of ERK1/2 (pERK1/2) and JNK, but not p38 MAP kinase. Interestingly, TNF-α production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes upon treatment with ginsenoside fractions. Next, we confirmed that DCs derived from CD14+ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the co-stimulatory molecules, CD80 and CD86. In the presence of ginsenoside fractions, expression of these co-stimulatory molecules decreased in LPS-treated DCs compared with LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, Gin-DCs treated with LPS could not induce proliferation and IFN-γ production of CD4+ T cells at co-culture of Gin-DCs with CD4+ T cells.Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of DCs treated with LPS, resulting in the down-regulation of CD4+ T cells.