Ethnopharmacological relevance: Wu-Ling-San (Hoelen Five Herb Formula) is a Chinese prescription used to promote water metabolism. Aim of the study: The present study was undertaken to characterize the effects of Wu-Ling-San on diabetic nephropathy. Materials and methods: Streptozotocin (STZ)-diabetic rats were orally administrated with Wu-Ling-San (0.5, 1.5, 2.5 g/(kg day)) once a day for 10 weeks. Changes in the renal function related parameters in plasma and urine were analyzed at the end of 10-week administration. Kidney was isolated for pathology histology, immunohistochemistry staining and Western blot analyses. Results: Wu-Ling-San (2.5 g/(kg day)) partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion rate, creatinine clearance, and glomerular mesangial matrix expansion were ameliorated by Wu-Ling-San. The increased expression of nuclear factor-kB as well as transforming growth factor-P I and the progressive accumulation of fibronectin in kidney of diabetic rats were attenuated by Wu-Ling-San. Not only the elevated levels of advanced glycation end products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, but also the higher levels of N-epsilon-(carboxymethyl)lysine and receptor for AGEs in kidney of diabetic rats were ameliorated by Wu-Ling-San. Conclusions: : Wu-Ling-San posses an anti-diabetic property with plasma glucose lowering action accompanied with amelioration of glycation-mediated renal damage. (C) 2009 Elsevier Ireland Ltd. All rights reserved.