The objective of this study is to investigate the anti-inflammatory effect of hydroxyethylpuerarin on focal brain ischemia injury in rats and to explore its mechanisms of action. After 24 h of reperfusion following 2 h of cerebral ischemia, the infiltration of neutrophils was observed by myeloperoxidase (MPO) activity determination, the expression of intercellular adhesion molecule-1(ICAM-1) was observed by western blot and reverse transcriptase-polymerase chain reaction(RT-PCR) analysis, and the nuclear translocation and DNA binding activity of nuclear factor-κB (NF-κB)were observed by western blot and electrophoretic mobility shift assay (EMSA). The results showed that hydroxyethylpuerarin could obviously inhibit the MPO activity and ICAM-1 expression following 2 hours of ischemia with 24 hours of reperfusion. The nuclear translocation and DNA binding activity were also decreased by hydroxyethylpuerarin treatment. These results suggested that hydroxyethylpuerarin could inhibit neutrophil-mediated inflammatory response after brain ischemia reperfusion in rats. This effect may be mediated by down-regulation of ICAM-1 and NF-κB activity.