Ginsenoside Rp1 is one of ginseng saponins with chemotherapeutic activity. In this study, we investigated the effects of Rp1 on spleen cells. Spleen is a major immune organ consisted of crucial immune cells, such as T lymphocytes, B lymphocytes, natural killer cells, and some antigen-presenting cells. Although the anti-tumor potential of Rp1 was studied, the effects of Rp1 on immune cells have not investigated yet. A viability assay using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT), flow cytometric analysis, Western blot analysis were used to detect cellular changes on Rp1-treated spleen cells. MTT assay showed that Rp1 decreased the viability of spleen cells. To further investigate the effects of Rp1 on activated spleen cells, we treated lipopolysaccharide (LPS) as a representative inflammatory agent and Rp1 on spleen cells in a combination. The surface expression levels of activation markers for lymphocytes, CD25 and CD69 were measured. Apoptotic analysis revealed the cytotoxic effects of Rp1 on both na?e and activated cells, and the expression pattern of some apoptosis-related proteins was correlated to apoptotic events of cells. Taken together, ginsenoside Rp1 increases the cellular death of spleen cells and also inhibits the LPS-induced activation of spleen cells.