<jats:title>Abstract</jats:title><jats:p>To investigate whether resveratrol could restore the lysophosphatidylcholine (LPC)‐induced loss of endothelium‐dependent relaxation in <jats:italic>in vitro</jats:italic> cultured rat aorta tissue, first the effect of resveratrol on the loss of EDR was examined in this preparation. The results showed that resveratrol effectively attenuated the inhibition of LPC (10 μm) on both endothelium‐derived relaxing factor (EDRF) and endothelium‐derived hyperpolarizing factor (EDHF) in a concentration‐dependent manner (1, 10, 100 μm). In addition, resveratrol inhibited elevated K<jats:sup>+</jats:sup>‐induced vascular contracture, but had no significant effects on ACh (1 μm)‐induced endothelium‐dependent relaxation (EDR). A similar tendency was also observed with PD 98059 (30 μm), a selective inhibitor of ERK. When the cells were exposed to LPC (20 μm) the mRNA expression of eNOS and COX‐1 mRNA were down‐regulated, followed by a local induction of iNOS and COX‐2. Resveratrol and PD 98059 successfully reversed the effects of LPC on relative mRNA expressions. Both resveratrol and PD 98059 inhibited the activation of ERK induced by LPC. These findings demonstrate that resveratrol can restore the LPC‐induced loss of EDR in rat aorta and protect the endothelium against LPC‐induced injuries via the inhibition of the inflammation‐like response. Copyright © 2010 John Wiley & Sons, Ltd.