Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance in people of all ages. Ginseng is also used to ameliorate menopausal systems. We investigated the estrogenic activity of Korean red ginseng (KRG) in a transient transfection system, using estrogen receptor (ER) and estrogen-responsive luciferase plasmids in MCF-7 cells. The extract activated both ERα and ERβ. KRG modulated the mRNA levels of estrogen-responsive genes such as pS2 and ESR1 and decreased the protein level of ERα. In order to examine in vivo estrogenic activity of KRG, sixteen female Sprague-Dawley rats separated into four groups were studied for nine weeks: non-ovariectomized (OVX) rats treated with olive oil, OVX rats treated with olive oil, OVX rats treated with 17-β-estradiol (E2) in olive oil, and OVX rats treated with KRG extract in olive oil. The experiments were repeated for three times and the data of twelve rats were combined. Body weight of OVX rats was greater than that of sham-operated control rats and was decreased by E2 treatment. Uterine weight increased after E2 treatment compared to OVX rats. However, no difference in body or uterine weight was observed with KRG intake. KRG induced reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, but not to the same degree as did E2 intake. These results show that KRG does contain estrogenic activity as manifested by in vitro study but the activity is not strong enough to elicit physiological responses.