Objective To investigate the effect of propofol on apoptosis at different time points after focal cerebral ischemia-reperfusion (I/R) in a rat model of reversible middle cerebral artery occlusion (MCAO). Methods Sixty male SD rats weighing 240-260g were randomly divided into 2 groups ( n = 30 each): propofol group received intraperitoneal (i. p.) propofol 80 mg ?kg before MCAO and control group received equal volume of normal saline instead of propofol. The animals were anesthetized with 10% chloral hydrate 350mg?kg-1 i.p. . The right external, internal and common carotid artery were exposed. A 4-0 nylon thread with rounded tip was inserted via external carotid artery into internal carotid artery and threaded cranially until resistance was felt. MCAO was maintained for 90 min before reperfusion. The animals were killed and brains removed for detection of apoptotic neurons using TUNEL staining combined with electronic microscopic examination at 3 h, 6 h, 24 h, 3 days, 5 days and 7 days after reperfusion was started ( n = 5 at each time point in both groups) . Results In control group the ratio of apoptotic neurons peaked at 24 h of reperfusion and then gradually decreased; while the ratio of TUNEL positive neurons kept on increasing indicating a shift from apoptosis to necrosis after 24 h reperfusion. The ratio of TUNEL positive neurons and apoptosis were significantly lower in propofol group than in control between 6 h to 3 days after reperfusion was started. Conclusion Propofol pretreatment attenuates apoptosis induced by focal cerebral I/R and the maximum effect is reached and maintained between 6 h to 3 days of reperfusion.