The effect of persimmon peel polyphenol (PPP) on high glucose-induced oxidative stress was investigated using LLG-PK1 cells, which is susceptible to oxidative stress. High-concentration glucose (30 mM) treatment induced LLC-PK1 cell death, but high molecular-PPP (HMPPP) and low molecular-PPP (LMPPP), at concentrations of 5 or 10 mu g/ml, significantly inhibited the high glucose-induced cytotoxicity. Furthermore, treatment with HMPPP or LMPPP dose-dependently reduced the intracellular reactive oxygen species level increased by 30 mM glucose. In addition, nitric oxide, superoxide and peroxynitrite levels were increased by 30 mM glucose treatment, but they were concentration-dependently inhibited by HMPPP or LMPPP treatment. High glucose levels induced the overexpressions of inducible nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) proteins, but HMPPP or LMPPP treatment reduced the overexpressions of these proteins. HMPPP or LMPPP also inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) induced by 30 mM glucose in LLG-PK1 cells. In particular, LMPPP exhibited stronger inhibitory activities on high glucose induced oxidative stress than HMPPP. These findings indicate the potential benefits of persimmon peel as a valuable source of antioxidants in the diabetic condition which will reduce the oxidative stress induced by hyperglycemia. (c) 2007 Elsevier Ltd. All rights reserved.