Abstract. Menopause occurs gradually and is characterized by increased susceptibility to developing mood disorders. Several studies have suggested that oxidative stress is implicated in the subsequent mood changes. It has been reported that quercetin glycosides may be effective due to their antioxidant abilities. The present work aimed to find out whether quercetin able to act against ovariectomy consequences and possible underlying mechanism(s). Animals were randomly divided into six groups of eight rats each. Group (1) Control group (2) Sham operated group (3) Ovariectomized (OVX) group (4) OVX-Isoquercetin-treated (10 mg/kg, i.p., dissolved in a DMSO/saline solution) group (5) OVX-estrogen-treated (subcutaneous implant of pellets (Innovative Research of America, Toledo, OH) containing 17β-estradiol (1.5 mg/8 wk) group (6) OVX-Isoquercetin-estrogen treated group. The treatments were initiated two week after both ovariectomy and sham operations and continued for four consecutive weeks. Tested parameters: oxidative stress markers (MDA, GSH, SOD), inflammatory cytokines (TNF-α, IL-6) and brain monoamines (dopamine, nor epinephrine, 5-HT). Results: Isoquercetin either alone or in combination with estrogen can improve: oxidative stress markers (MDA, GSH, SOD), inflammatory cytokines (TNF-α, IL-6) and brain monoamines (dopamine, nor epinephrine, 5- HT). Combination of both isoquercetin & estrogen gives the best results in most of the tested parameters especially in normalizing IL-6 level. Concerning serotonin estrogen was as good as the combined drugs. Conclusion: Isoquercetin has an additive role with estrogen to maintain healthy brain tissue for production of normal monoamine levels.