Objective: Quercetin is a phytoestrogen that exerts both in vitro agonistic and antagonistic activities on estrogen receptors. The present study evaluated the in vivo estrogen-like activity of quercetin on the reproductive organs of female rats. For this purpose, a partial estrogen agonist tamoxifen (TMX) and an estrogen antagonist fulvestrant (FLV) were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. 4-Vinylcyclohexene dioxide (VCD) was used to induce primary ovarian failure in rats. Materials and Methods: In experiment 1, immature female rats (21-22 days old) were treated with a vehicle (control), quercetin (10, 30, and 90 mg/kg), 10 mg/kg of quercetin (Q10)+TMX, Q10+ FLV, 17?-estradiol (17?E), 17?E+TMX, or 17?E+FLV. In experiment 2, prepubertal female rats (28-29 days old) were treated with a vehicle (dimethyl sulfoxide), VCD-alone, VCD+Q10, or VCD+17?E. A uterotrophic assay and histological analysis of uteri were performed. The partial estrogen agonist TMX and the estrogen antagonist FLV were used to mimic and antagonize the effects of estrogen on uterine tissue, respectively. VCD was used to induce primary ovarian failure in rats.Results: In immature female rats, the uterine weight was significantly higher in animals treated with Q10 compared to those treated with the vehicle. Although TMX did not result in a significant change, FLV significantly decreased the uterine weight in Q10-treated rats. In prepubertal female rats, the uterine weight significantly decreased in VCD±Q10- or 17?E-treated animals compared that in VCD-treated animals. Although the endometrial thickness was unchanged in Q10-treated animals, it was significantly decreased in the Q10+FLV-treated animals. VCD significantly decreased the endometrial thickness, which was prevented by Q10. Conclusion: Quercetin may have a dose-dependent and biphasic effect on the uterus by modulating estrogen receptors.