Didymin protected against high glucose (HG)-induced human umbilical vein endothelial cells by modulating the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion protein (VCAM)-1, and regulating nuclear factor kappa B (NF-κB)-mediated inflammatory cytokines and chemokines. Didymin prevented HG-induced endothelial dysfunction and death via antioxidative and anti-inflammatory activities. This evidence concerns the gene VCAM1 and endothelial dysfunction.