The present study was designed to identify the histopathological effect of fluoxetine (fluoxetine hydrochloride) on the pregnant mice brain and their fetuses as well as recording weight changes at doses of 60 and 80 mg/kg of body weight which were administrated to the pregnant mice from the 7th
up to the 18th
day of pregnancy and once a day. The results showed histopathological lesions in the adult pregnant mice brain at the dose of 60 mg/kg. induced massive necrotic area of neurons in the cerebral cortex, necrosis of the molecular layer cells while the dose of 80 mg/kg the changes include vasogenic edema in the sub cortical area, severe degeneration and necrosis of the cortex. The lesions in cerebellum were more severe than recorded in the cerebrum. The results also showed the presence of many lesions in the fetus brain at the dose 60 mg/kg and they were degeneration, necrosis of many neurons in the cerebrum while at the dose of 80 mg/kg. There were increase of degeneration and necrosis in the cortical area of fetus brain. In conclusion, the use of fluoxetine in pregnant mice caused decrease in body weight and Histopathological changes in the brain of both of the mothers and their embryos, thus the use of antidepressant by pregnant woman can be harmful for the mothers and the fetus.