Glycyrrhizae radix (GR) is an herbal medicine commonly used in East Asia for treating a variety of diseases, including stomach disorders. In this study, the antidepressant-like activity of GR was investigated using the forced swimming test (FST) in rats. After the FST, the expression of c-Fos and corticotrophin releasing factor (CRF) was assessed by immunochemistry of brain samples from the paraventricular nucleus of the hypothalamus (PVN). The results of the FST showed that a high dose (400 mg/kg) of extract was very effective in reducing immobility(P<0.01), and increased climbing. In addition, treatment with GR (400 mg/kg) significantly decreased the expression of c-Fos and CRF in the PVN, compared to controls. In conclusion, the findings of this study demonstrated that GR effectively reduced behavioral and physiological depression responses in an animal model of depression, suggesting that GR might be useful in the treatment of clinical depression.