Objective: Byakkokaninjinto (BKN) is clinically used for conditions associated with thirst, polyuria, or cutaneous pruritus.Recently, it has also been used for improving thirst and polyuria observed in diabetes as well as pruritus associated with excessively dry skin. The aim of this study was to investigate aquaporins (AQP) in order to obtain scientific evidence regarding the mechanisms of BKN's effect. Results: Treatment with BKN in a diabetic model of KKAy mice did not affect blood glucose but reduced both water intake and urine volume. Although the AQP5 level in the salivary glands remained unchanged, the AQP2 level in the kidneys increased significantly. This suggests that BKN causes an increase in AQP2 expression in the kidney, thereby suppressing polyuria as well as the associated thirst caused by diabetes. BKN was also shown to increase the expression of AQP3 in skin, which may suppress skin dryness and improve pruritus. In addition, Gypsum fibrosum (GF), the principal component of BKN, did not affect kidney AQP2 expression but increased skin AQP3 expression. The active ingredient of GF, CaSO 4 , was also shown to increase AQP3 expression via protein kinase C activation and to enhance phosphorylation of cAMP response element-binding protein by increasing the Ca 2+ concentration in skin. Conclusion: Although there are many herbal medicines that are effective for correcting abnormal water metabolism, little is known regarding the mechanism of this activity. This study highlights the scientific basis of the effect of herbal medicines in improving water metabolism, with AQP as the primary targets.