Objective To study the role of extracellular signal-regulated kinase （ERK） in cerebral ischemia and the mechanism of protective effects of U0126 （1

4-diamino-2

3-dicyano-1

4-bis[2-aminophenylthio] butadiene） on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion （MCAO） by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 （pERK1/2）

phos-phorylated mitogen activated protein kinase kinase （pMEK）

and phosphorylated Elk-1 （pElk-1） was assessed by Western blot analysis and immunohistochemistry. Interleukin （IL）-1βmRNA level was measured by ribonuclease protection assay. Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1βmRNA increased after 1 and 2 hours of MCAO. After injection of U0126

it was down-regulated during 1 to 4 hours after MCAO. Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK

pERK1/2

and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1βmRNA via the inhibition of ERK pathway.