This study was performed to compare the effects of Chai-hu-gui-zhi-gan-jiang-tang (Saiko-keishi-kankyo-to), an herbal medicine, in improving depressed mood and on plasma interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) concentrations with those of anti-depressants in peri- and post-menopausal women. Ninety patients complaining of menopausal symptoms including insomnia who were diagnosed with mood disorder based on DSM-IV were recruited and separated into two groups (Chai-hu-gui-zhi-gan-jiang-tang group was selected on the basis of SHO for 42 cases, while anti-depressants were used for 48 cases), and plasma IL-6 and sIL-6R concentrations were determined before and after three months of the treatment. There were no significant differences in the decrease in both climacteric and Hamilton depression score after treatment between the two groups. Plasma IL-6 and sIL-6R concentrations were significantly lower in the Chai-hu-gui-zhi-gan-jiang-tang group (-34.8 +/- 15.5% and -22.4 +/- 14.6%, respectively) than in the anti-depressant group (7.5 +/- 4.8% and 2.4 +/- 3.8%, respectively) after 3 months of treatment. Correlations between rate of decrease in climacteric score and plasma IL-6 (R = 0.498, P = 0.0056) and sIL-6R (R = 0.512, P = 0.0045) concentrations were observed. Chai-hu-gui-zhi-gan-jiang-tang reduced plasma IL-6 and sIL-6R concentrations in relation to improvement of depressed mood during treatment. The findings of this study suggest that Chai-hu-gui-zhi-gan-jiang-tang has the potential to decrease morbidity by alleviation of stress reactions in peri- and post-menopausal women.