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Background: Postpartum depression (PPD) is a major depressive disorder and one of the most common complications of childbearing. PPD has a serious impact on the quality of life of all family members. Oxidative stress is one of the contributing factors in pathophysiology of major depression. Thus, drugs with potential antioxidant action could be an attractive target for treatment of depressive disorders. Matricaria Chamomilla and Selenium are natural sources of antioxidant. The aim of this study was to evaluate effects of oral administration of Matricaria Chamomilla aqueous extract and Selenium on experimental model of progesterone-induced postpartum depression and plasma oxidant-antioxidant system in mice. Methods: Seventy adult female mice in seven groups were used in this study. All animals received daily injections of progesterone 5 mg/kg intraperitoneally for five days after which progesterone was withdrawn for three days. After modelling postpartum depression with progesterone withdrawal, Matricaria Chamomilla 300 mg/kg and Selenium 0.1 mg/kg and their combination were administered via gavage and imipramine 15 mg/kg was administered intraperitoneally one hour before open field and forced swimming test (FST). In order to investigate the role of oxidant-antioxidant system, PAB and MDA were meatured. Results: All the treatment groups and the standard group spent less immobility time than the control group (P