Adhesion of leukocytes to endothelial cells plays an important role in the progression of neuroinflammation. Therefore, suppression of adhesion molecules expression in brain endothelial cells may contribute to inhibition of neuroinflammation. Chrysin (5,7-dihydroxyflavone) is a flavonoid component of propolis, blue passion flower and fruits. In the present study, we examined the effects of chrysin on lipopolysaccharide-induced expression of VCAM-1 in mouse cerebral vascular endothelial (bEnd.3) cells. In bEnd.3 cells, LPS increased mRNA expression of VCAM-1 in time-dependent manner. Crysin significantly decreased LPS-induced mRNA expression of VCAM-1. Chrysin also remarkably reduced protein expression of VCAM-1 in a concentration-dependent manner. Furthermore, chrysin dramatically blocked adhesion of U937 (monocytes) to bEnd.3 cells induced by LPS. Nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which are activated by LPS, were significantly inhibited by chrysin. These results indicate that chrysin inhibits the expression of VCAM-1 in brain endothelial cells through inhibition of NF-κB translocation and MAPK pathway, resulting in an attenuation of leukocytes adhesion to endothelial cells. The anti-neuroinflammatory effects of chrysin suggests a possible therapeutic application of this agent in neurodegenerative diseases such as septic encephalopathy, multiple sclerosis and allergic encephalomyelitis.