Abstract: Background and Objective: Stress is known to play a causal role in several neuropsychiatric disorders. Trolox has been reported to show potent antioxidant activity against reactive oxygen species. The aim of this study was to investigate the effect of trolox on the behaviour and biochemical parameters of mice exposed to immobilization stress. Materials and Methods: The mice were subjected to 6 h of immobilization stress daily for 7 consecutive days. The 48 mice were randomly divided into 6 groups with 8 mice each: (I) Control, (II) Immobilization (IM), (III) Immobilization+Trolox (IM+T), (IV) Immobilization+Fluoxetine (IM+F), (V) Immobilization+Trolox+Fluoxetine (IM+T+F) and (VI) Trolox (T). At the end of day 7, open field test (OFT) and forced swimming test (FST) were performed to assess the locomotor activity and anxiety-like behaviour in mice. After the completion of these tests, brain tissue samples were removed for biochemical analysis. Results: The OFT and FST results indicated that the incidences of anxiety-like and depression-like behaviour were significantly lower in the IM+T group compared to the IM group. A significant improvement was observed in the groups treated with trolox for the catalase, total oxidant status, total antioxidant status and oxidative stress index values deteriorated by immobilization. Conclusion: The results implicated that antioxidant molecules such as trolox can lead to favourable outcomes in the treatment of oxidative damage either in isolation or in combination with classic treatment methods.