Sogeunjung-tang (S-tang) is a traditional Korean medicine that has been used for the therapy of anxiety disorder in a variety of clinical situations. However, no study has investigated this effect. The aim of this study was to investigate the effectiveness of S-tang for reducing depression in animal model. The antidepressant effect of S-tang was investigated in ICR mice by using forced swimming test (FST). After FST, we analyzed the blood biochemical parameters from blood. The immobility time was significantly decreased in the S-tang oral administration or pharmaceutical acupuncture group compared with the control group at 14 days (p < 0.05). The anti-depressant effect of S-tang was higher than that of fluoxetine (a classical anti-depressant). S-tang or fluoxetine significantly decreased the creatine kinase and lactate dehydrogenase level compared with the control group (p < 0.05) but not glucose, protein, and blood urea nitrogen level. Further investigation of S-tang as a potential pharmacologic agent in the management of depression related anxiety is warranted.