The in-vitro immunomodulatory function of murine natural-killer (NK) cells induced by red-ginseng acidic polysaccharide (RGAP) in ovariectomized (OVX) rats was examined in this study. The IL-2-induced NK cell activity was significantly decreased in the OVX rats compared to the sham groups, but the normally induced NK cell activity was not. RGAP, however, increased the NK cell activity in both groups, and this effect involved iNOS expression. The inhibition of iNOS activity did not increase the NK cell cytotoxicity by RGAP in the OVX rats. The data that were obtained also demonstrated that the expression of iNOS was increased in the spleen of the OVX rats. These results indicate that RGAP increases the tumoricidal activity of the NK cell in the OVX rats, which is a primed or activated state of innate immune cells resulting from the changes in cytokine production induced by estrogen-deficient stress. Therefore, RGAP has a synergistic effect on the NK cell activities, which are regulated by the iNOS signals in OVX rats. This suggests that RGAP is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in OVX rats.