Objective To investigate the effect of propofol on the expression of c-fos protein and c-fos mRNA in hippocampus during global cerebral ischemia-reperfusion in rats. Methods Forty male Wistar rats weighing 250-320 g were randomly allocated to one of five groups: group A received sham operation ( n = 8); group B received ischemia-reperfusion (I-R n = 8); group C received intraperitoneal propofol 50 mg?kg-1(C1 n = 8) or 100 mg@kg-1(C2 n = 8) or 150 mg2kg-1(C3 n = 8) 10 min before I-R. The animals were anesthetized with intraperitoneal pentobarbital 40 mg?kg-1.Vertebral arteries were surgically exposed and permanently occluded by coagulation. Bilateral common carotid arteries were exposed. 4-0 silk suture was placed around the arteries. Global cerebral ischemia was induced by lighting the suture for 10 min which was then loosened for reperfusion. At the end of 60 min reperfusion the animals were decapitated on ice and brain was immediately removed. Different brain tissues were either kept in liquid nitrogen ( - 80℃) or fixed in 10% formalin. The changes in c-fos protein in brain was evaluated by immuno-histochemical methods and c-fos mRNA expression in hippocampus was detected using semiquantitative RT-PCR technique.Results The c-fos expression was minimal in sham operation group. I-R induced significant increase in the expression of c-fos protein and c-fos mRNA and propofol significantly inhibited the increase in c-fos expression induced by I-R. The levels of c-fos expression were higher in group C1 than that in group C2 (P 0.05) . Conclusion The study shows that propofol can significantly inhibit expression of c-fos protein and c-fos mRNA induced by global cerebral I-R.