The hippocampus is one of the stress-sensitive limbic structures implicated in the pathophysiology of mood associated disorders including depression. Convergent lines of research implicate the hippocampus in the pathogenesis of major depression disorders (MDD). Fluoxetine, a selective serotonin inhibitor (SSRI), has been effectively used in the clinical management of MDD. However, little is known about the effects of antidepressant fluoxetine on the electrical brain wave of the hippocampus. This study aimed to investigate the effect of fluoxetine on hippocampal local field potential (LFP). Male Swiss Albino (ICR) mice were implanted with an intracranial electrode into the hippocampus for LFP recording. Following fluoxetine (20 mg/kg) treatment, hippocampal LFP signals were recorded and analyzed in comparison to the control levels. Raw LFP signals were then transformed into power spectral densities (PSD) and expressed as the percentages of total power. The results revealed that fluoxetine significantly decreased alpha2 (9.8 – 12.7 Hz) and beta1 (13.2 – 18.1 Hz) powers and pronouncedly increased gamma1 (30.8 – 43.0 Hz) power in particular with the maximum response at 1 hour following the treatment. Suppression of slow frequency and enhancement of specific gamma power spectrum indicated the hippocampal activation status which might be associated with the increasing of monoamine neurotransmission. In conclusion, the results from this study suggested that fluoxetine may involve neurotransmitter systems that produce an alteration of hippocampal local field potential.