Background: Olive oil (OO) has neuroprotective effects and is inversely associated with depression risk. However, the role of neurotransmitter systems in the pathophysiology of depression is still unclear. Objectives: In the present study, the antidepressant effect of olive oil and the underlying neurochemical mechanism were investigated. Materials and methods: Twenty eight male albino rats were allocated into four equal groups: Control group, OO-supplemented group (OO was given in a daily dose of 300 μl/kg by gavage 5 days a week for 2 consecutive weeks, restraint stress (RS) group, and OO+RS group. Forced swim test was performed and immobility time was measured. Serotonin, malondialdehyde (MDA) and glutathione peroxidase (GPx) in the brain stem homogenate, and cortisol level in the serum were measured. Results: Restraint stress group showed significant decrease in immobility time during forced swimming test, along with significant increase in serum cortisol, serotonin and MDA, and significant decrease in GPx. In the OO+RS group, immobility time was significantly reduced compared to restraint stress group and compared to control group. Cortisol, serotonin and MDA decreased and GPx increased. Conclusion: Olive oil has antidepressant potential which could be mediated via its antioxidant not its neurochemical effects.