The effect of cadmium chloride (CdCl₂) on the expression of E-cadherin was examined in bEnd.3 mouse brain endothelial cells. CdCl₂ induced PGE₂ release, which were blocked by non-steroidal antiinflamatory drugs (NSAIDs) such as indomethacin and NS398 indicating the expression of COX-2 might contribute to PGE₂ production. CdCl₂ decreased the expression of E-cadherin, but not VE-cadherin at levels of mRNA and protein. Reduced expression level of E-cadherin was restored by NSAIDs, which was reversed by the addition of PGE₂. CdCl₂-induced decrease of E-cadherin level was also recovered by antioxidants including N-acetylcyteine (NAC) and trolox. Together with previous report which showed CdCl₂ induced COX-2 expression in a cellular oxidative stress dependent manner, these data suggest that CdCl₂ decreases E-cadherin expression through induction of cellular oxidative stress and in turn COX-2 expression in brain endothelial cells.