Back Ground: Estrogen is the sex hormone that causes the development and maintenance female secondary sexual characters. Post menopausal women increasing in vulnerable to depression due to the reduced estrogen production. The activity of estrogen on serotonin has anti depressant characteristics. A higher level serotonin activity is associated with Positive mood while decreased activity is associated with depressive mood. Estrogen boosts the activity of serotonin. Objectives: To determine the brain serotonin and its major metabolite 5HIAA in ovariectomized rats at different day intervals and after estradiol treatment. Methodology: Female albino rats of wister strain where ovariectomized and treated with ethanyl estradiol, Brain serotonin and 5HIAA was estimated by Fluoremetric method. Data was analysed by student’s t test. Result: Reduction in serotonin and 5HIAA level in Hypothalamus, striatum and pons medulla after ovariectomy and increased in estradiol treated rats. Conclusion: Estrogen may be used as effective anti depressant after further studies.