Rhei Rhizoma (RR) and Moutan cortex (MC) have been reported to have anti-inflammatory effects. However, little is known about the effects of RR and MC on endothelial inflammation and insulin resistance (IR). This study aims to investigate whether the water extracts of RR and MC could exert protection against palmitic acid (PA)-induced inflammation and IR in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 6 h with RR or MC, and then exposed to PA for 24 h. The levels of interleukin-6 (IL-6) and tumor necrosis factor-${alpha}$ (TNF-${alpha}$) were determined by enzyme-linked immunosorbant assay kits. Western blot analysis was performed for activation of nuclear factor-${kappa}B$ (NF-${kappa}B$) and insulin receptor substrate-1 (IRS-1). In HUVECs stimulated with PA, both RR and MC significantly inhibited the production of TNF-${alpha}$ and IL-6 and the activation of NF-${kappa}B$. At the same concentrations, the inhibitory effects of RR were more potent than those of MC. PA reduced insulin-induced phosphorylation of IRS-1, which was reversed by RR and MC. The results suggest that RR and MC are effective in inhibiting PA-associated endothelial inflammation and ameliorating IR by beneficial regulation of NF-${kappa}B$ and IRS-1 activation.