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ABSTRACT: Resveratrol (Res) displays potent anti-oxidant activity and is a selective estrogen receptor modulator. The aim of the present study is to investigate whether Res consumption protects ovariectomized (OVX) rats chronically treated with D-galactose (D-gal) from developing memory decline and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with estradiol replacement therapy. Rats were divided into 6 groups: 1) Sham control group; 2) OVX+D-gal 100mg/kg group (OVX+D-gal); 3-5) OVX, D-gal and Res 20, 40, 80 mg/kg treated groups; and 6) OVX, D-gal and estradiol valerate 0.8 mg/kg treated group (ET). Twelve weeks later, in a Morris water maze test, the OVX+D-gal rats exhibited a significant memory impairment compared with the Sham control rats, which was accompanied by decreased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activities and an increased thiobarbituric acid reactive substances (TBARS) level in the serum. In addition, the TBARS and protein carbonylation levels increased in the hippocampus. The beneficial roles of the 40 and 80 mg/kg Res treatments were manifested in the prevention of memory decline and markedly decreased oxidant stress indices. The disruption of the cristae in the mitochondria and the irregular nuclei and condensed chromatin in the pyramidal cells of the hippocampal CA1 region were also reduced after Res treatment. Furthermore, edema in the endometrium and lymphocyte infiltration was avoided in all three of the Res-treated groups compared with the ET group. These results suggest that Res is useful not only in protecting OVX+D-gal rats from developing memory decline by increasing the anti-oxidation but also in avoiding the effects on the uterus.