There is increasing concern on the adverse effect of genistein on fertility(1). This compound, known for its oestrogenic activity, can be found mainly in soy based product such as tofu and soy-base milk(2). It possesses a similar structure with oestradiol-17β, therefore able to bind to estrogen receptor (ER) α and β, which are widely found in the uterus(3). We hypothesize that genistein can interfere uterine fluid environment and implantation, contributing to impaired fertility. The aim of this study is to investigate the effect of genistein at different doses on the uterine fluid volume, pH and its ionic compositions. Additionally, histological changes in the uterus and the number of pups at the implantation sites after genistein administration were also determined. Adult female SD rats, weighing 250-300 g were ovariectomized ten days prior to the experiment. The animals were anaesthetized by intraperitoneal injection of 0.1 ml (80 ml/kg) ketamine (Velatar) and 0.15 ml (10 ml/kg) xylazine hydrochloride (Rompun). In vivo perfusion study was performed under continuously monitored per-rectal temperature. The animals were divided into 8 groups (n=6 per group), which were treated with peanut oil (vehicle), oestradiol-3 benzoat (2µg/ml) and genistein (0.5, 5, 10, 25, 50 and 100 mg/kg/day). The collected fluid was analyzed for the changes in the volume, pH and its electrolytes content (Na+, Cl- & K+). In another series of experiment using ICR mice, genistein was injected subcutaneously at day 1 of pregnancy (determined by the presence of vaginal plug). The number of pups found at the implantation sites was counted on day 8. Data are expressed in mean ± SEM and analyzed using student t-test. Our results showed that genistein at higher doses (50 and 100 mg/kg/day) caused an increase in the uterine luminal fluid volume, pH, Na+ and Cl- concentration and reduction in K+ concentration. Similar effects were seen in oestradiol treated rats. The morphological changes of increased glandular proliferation was seen in both genistein (50 & 100 mg/kg/day) and oestradiol treated rats. There was a decrease in the number of pups with increasing doses of genistein and no pups were seen at the highest dose. In conclusion, high doses of genistein mimic the effects of oestradiol on the uterus. These findings suggest that genistein may have an effect on fertility by affecting the luminal fluid environment.