Resveratrol has shown array of biological actions, and is under clinical development for various disease conditions. The etiology of diabetic neuropathy revolves around oxidative stress. AGE formation, lipid peroxidation etc. All these stimulate inflammatory processes and NF-kappa B cascade is considered as one of the major players of inflammatory response. Activation of NF-kappa B results in elevated levels of inflammatory mediators. COX-2 and TNF-alpha activity have also been correlated with inflammatory damage in the pathophysiology of diabetic neuropathy (ON). Therefore we investigated the effect of resveratrol on NF-kappa B inflammatory cascade, COX-2, TNF-alpha and IL-6 levels in experimental DN. We found that resveratrol protected against various functional and behavioral deficits in diabetic neuropathy in line with our earlier published reports. In this study we found that the resveratrol treatment decreased the expression of p65 and I kappa B-alpha in treated rats. Treatment also ameliorated the elevated levels of TNF-alpha, IL-6 and COX-2. Resveratrol treatment produced significant decrease in nerve MDA levels in treated animals which may also be contributing to reduction in neuro-inflammation. This study confirms the NF-kappa B inhibitory activity and anti-inflammatory activity of resveratrol which may contribute to neuroprotection in diabetic neuropathy apart from its antioxidant effect. (C) 2010 Elsevier Inc. All rights reserved.