Abstract: OBJECTIVE To evaluate the effects of fluoxetine on the methylglyoxal(MGO) induced injury in the cultured human brain microvascular endothelial cells(HBMEC). METHODS In the cultured HBMEC, fluoxetine was added before MGO deprivation injury. Cell injury was measured by MTT, SOD activity and MDA content. Cell apoptosis was measured by caspase-3 activity and annexin V/PI formation. RESULTS Fluoxetine dose-dependently protected MGO induced HBMEC injury. Fluoxetine at 10^-5 mol·L^-1 manifested the maximum effects. MGO decreased SOD activity and increased MDA content, which were reversed by pretreatment of fluoxetine (10^-5 mol·L^-1). Furthermore, fluoxetine (10^-5 mol·L^-1) also decreased MGO induced caspase-3 activity increasing and annexin V/PI formation. CONCLUSION Fluoxetine protects MGO induced injury in the cultured HBMEC, which may be involved its anti-oxidation and anti-apoptosis activity.