Objective To evaluate the effects of propofol pretreatment on blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol. Methods Twenty-four male SD rats aged 5-6 months, weighing 300-350 g were randomly divided into 3 groups (n = 8 each) :Ⅰ control group; Ⅱ small-dose propofol group and Ⅲ large dose propofol group. The animals were anesthetized with isoflurane, tracheostomized and mechanically ventilated (VT = 10-15 ml2kg-1, RR = 45-55 bpm) . PETCO2 was maintained at 35-45 mm Hg. Right femoral artery and vein were cannulated for BP and HR monitoring, blood sampling and drug administration. Right internal and external carotid arteries were exposed. External carotid artery was ligated and internal carotid artery was cannulated for mannitol administration. In the two propofol groups propofol 20 mg?kg-1 or 40 mg2kg-1 was injected slowly over 20 min. Ten minutes after propofol injection was started, 20% mannitol was infused at 0.25 ml?kg-1?s-1 for 30 seconds. Two minutes after intracarotid mannitol injection 20 uCi 14 C-AIB was injected via femoral vein in all three groups. Five minutes after 14C-AIB injection, 20 uCi 3H-Dextran was injected via femoral vein. Arterial blood samples were taken within 10 min after 14C-AIB injection every 20 seconds for 2 min then after an interval of 2 min every min. Altogether 14 blood samples were taken. The animals were then decapitated and cerebral cortex, cerebellum, pons and basal ganglia were separated. The radioactivity of plasma and brain specimens was counted with a liquid scintillation counter. The blood-brain Ki for 14C-AIB was calculated. Results The Ki of the ipsilateral cortex where mannitol was injected was 4.9 times as much as that of the contralateral cortex in control group, 3-5 times in small dose propofol group and 2.5 times in large dose propofol group respectively (P