OBJECTIVE: To define the effects of Xanthoceras sorbifolia (EXS) on vascular inflammation and the mechanisms in endothelial cells. METHODS: Vascular protective effects of an ethanol extract of seeds from EXS (1-50 μg/mL) against tumor necrosis factor-α (TNF-α)-induced vascular inflammation were examined in human umbilical vein endothelial cells (HUVECs). RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin, in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB (NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species (ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP (HO-1 inhibitor)- and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX (CoPP) (HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP- and of HO-1 siRNA-treated cells but increased by CoPP. CONCLUSION: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-¦ÊB/ROS pathway and activation of the Nrf-2/HO-1 pathway.