Aim of the study Zhuling, sclerotia of Polyporus umbellatus FRIES, a Traditional Chinese Medicine, has long been used as a diuretic The aim of the present study was to evaluate the diuretic effect on the urinary electrolyte concentration (Na+, K+, and Cl-) and regulation of the relative mRNA expression of aquaporin-1 (AQP1), aquaporin-2 (AQP2), aquaporin-3 (AQP3) and vasopressin V-2 receptor (V2R) postoral administration of sclerotia of Polyporus umbellata aqueous extract in normal rats. Materials and methods Aqueous extract of sclerotia of Polyporus umbellatus (50 mg/kg, 250 mg/kg, 500 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated orally to male SD rats and their urine output was quantified and collected 2411 and 8 days after the treatment The kidney medulla AQP1, AQP2, AQP3 and V2R mRNA relative expressions were measured with RT-PCR Results: After single close of the exact of sclerotia of Polyporus umbellata. urine output was found to be significantly increased, which began at 4 h. and at 24 h after the treatment, the sclerotia of Polyporus umbellatus extract and furosemide treatment produced the similar total volume of urine exacted The extract increases urinary levels of Na+, K+, and CI-, to about the same extent. while furosemide increased urinary levels of Na+ and Cl-. After the 8-day doses, all two substances induced significant diuresis, natriuresis and chloriuresis These two substances do not regulate the AQP1 and AQP3 mRNA level in normal rat kidney medulla The AQP2 mRNA level of sclerotia of Polyporus umbellata extract was down-regulated significantly, the V2R mRNA level of sclerotia of Polyporus umbellata extract 50 mg/kg dose group and 250 mg/kg close group were down-regulated significantly too Interestingly, the low-dose group had higher effect on regulation of AQP2 and V2R mRNA level Conclusion Aqueous extract of sclerotia of Polyporus umbellatus has conspicuous diuretic effect confirming its ethnopharmacological use. From the pattern of excretion of water, sodium, potassium. chlorine, AQP2 and V2R mRNA level, it may be logically concluded that it has effect from down-regulating AQP2, and down-regulate AQP2 by down-regulating V2R. (C) 2010 Elsevier Ireland Ltd All rights reserved