Fluoxetine Hydrochloride a potential antidepressant drug with high affinity of serotonin (5-hydroxytryptamine), dopamine (DA) and noradrenaline (NA) in selected regions of the rat brain.Fluoxetine administration enhances extracellular serotonin (5-HT) in the frontal cortex and no parallel changes in the concentration of dopamine Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Hence the purpose of present study is to determine effect of Fluoxetine hydrochloride microsphere prepared by using combination of Eudragit RS and HPMC K4polymer on monoamine concentration in rat brain. Our main aim is to study relationship such as serotonin (5HT), dopamine (DA) and nonadrenaline (NA)in the brain of rat It showed that significant reduction occur in monoamine formation in brain of rat. Thus study suggest that prepared Olanzepine microsphere showed decreased the monoamine on rat brain