Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions and calcitriol may improve the cardiovascular complications. Therefore we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor kappa B (NFB) in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-HSA. AGE-HSA induced a decrease in nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA treated endothelial cells, improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of IL-6 mRNA in presence of AGE-HSA was also blunted by calcitriol. The NFB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kappa B (IB) and an increase in p-IB levels. Addition of calcitriol blunted the AGEs induced elevation of NFB-p65 DNA binding activity, a phenomenon related to an increased expression of IB. This increase was correlated to a declined p-IB levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities.