BACKGROUND Ginseng has been widely used for hundreds of years in both China and other countries. It is well accepted that the pharmacological effects of ginseng are attributed to ginsenosides. Ginsenoside Re is one of the active ingredients in ginseng. The present study was carried out to characterize the toxicity of ginsenoside Re after repeated oral administration in Sprague-Dawley rats. METHODS Rats (60 males, 60 females) were administrated ginsenoside Re orally in 0, 38, 113, or 375 mg/kg/day doses for 26 weeks (n=15/group each sex). Clinical signs, mortality, body weights, feed consumption, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined at the end of the test period, as well as after the 4-week recovery period. RESULTS Ginsenoside Re did not induce death, adverse effects or dose-dependent changes in feed consumption, or body weight gain. Some statistically significant differences were observed in hematological and biochemical parameters, as well as in body weights of rats treated with ginsenoside Re. However, there was no abnormality of any organs noted in both gross and histopathological examinations. CONCLUSIONS Ginsenoside Re is well tolerated up to a 375 mg/kg/day oral dosage level and non-toxic in both male and female rats.