Luteolin (LUT) is a flavonoid contained in many plants and with a variety of known pharmacological properties such as anti-inflammatory, anti-anxiety, and memory-improving effects, suggesting that LUT penetrates into the brain.In the present study, we investigated the effects of LUT on the behaviors of chronic unpredictable mild stress (CUMS) induced depression model mice and to elucidate the related possible mechanisms.With the exposure to stressor once daily for consecutive 5 weeks, LUT were administered via gastric intubation to mice at doses of 50 mg/kg or 100 mg/kg once daily for consecutive 3 weeks from the 3rd week.The results showed that CUMS significantly decreased the levels of serum 5-HT and NE, and the activities of superoxide dismutase (SOD) and catalase (CAT), with an increase in lipid peroxidation level as well as a reduction in glutathione (GSH) level and an elevation in the production of malondialdehyde (MDA) in hippocampus.CUMS also reduced openfield activity, sucrose consumption, as well as increased immobility duration in FST and TST.LUT administration could effectively reverse the alterations in the concentrations of NE and 5-HT, lessen the level of MDA, elevate the activities of SOD and CAT, and the level of GSH, and inhibit lipid peroxidation.Moreover, LUT could effectively reverse alterations in immobility duration, sucrose consumption and open-field activity.In conclusion, the present study demonstrated administration of LUT has exhibited significant antidepressant-like effects in mice with CUMS-induced depression, which might be related to the alteration of monoaminergic response and antioxidant defenses.