Abstract. – Background and Objectives: A number of studies have shown that nicotine has an antidepressant-like effect. The prevalence of smoking is much higher in people suffering from depression. In addition, the administration of nicotine from transdermal nicotine patch can exert antidepressant activity in nonsmokers and the continuous infusion of nicotine to rats attenuates learned helplessness, a putative behavioral model of depression. The aim of the present study is to elucidate the neurochemical effect of nicotine on monoamine levels in the cerebral cortex and hippocampus of reserpinized rats as a model of depression. Materials and Methods: In the present study, rats were divided into control animals treated with saline and reserpinized group which received a daily i.p injection of reserpine for 15 days to establish the animal model of depression. Starting from the 16th day, the reserpinized rats were divided into reserpinized rats, and reserpinized rats treated daily with nicotine (0.4 mg/kg) for 15 and 30 days. After decapitation, the cerebral cortex and hippocampus of each rat were dissected out. The levels of monoamine neurotransmitters (serotonin, norepinephrine and dopamine) were measured in each area using a spectrofluorimeter. Results: The daily i.p injection of reserpine induced a significant decrease in monoamine levels in the cortex and hippocampus. Nicotine administration restored the changes in monoamine neurotransmitters induced by reserpine in both areas after 30 days. Discussion: The data of the present study suggest that the antidepressant-like effect of nicotine could be mediated by the effect of nicotine on monoamine neurotransmitters in the cortex and hippocampus of rat brain.