Objective　By observing the effect of adenosine pretreatment on BBB permeability and AQP4 expression in the brain around the infarct area，the protective effect of adenosine pretreatment on brain and its possible mechanism were discussed from the perspective of BBB. Methods　SD （Sprague Dewley） rats were randomly divided into control group （F Group），model group （IR group） and adenosine preconditioning group （AP group）. Each group was further divided into 4 subgroups：6 h，24 h，48 h and 72 h groups. Brain water content was measured by dry wet weight method；BBB permeability was analyzed by Evans blue （EB） permeation method；AQP4 protein expression was detected by immunohistochemistry at different time points. Results　①The brain water content in AP group was significantly lower than that in IR group （P<0.05）. ②The amount of EB exudation in IR group and AP group was significantly higher than that in F group，the difference was statistically significant （P<0.05）；the EB exudation volume of AP group was significantly lower than that of IR group，but higher than that of F group，with significant difference（P<0.05）. ③AQP4 expression in IR group and AP group was higher than that in F group（P<0.05）；AQP4 expression in AP group was significantly lower than that in IR group（P<0.05）. ④Compared with IR group and AP group，EB exudation reached the peak at 48 h，then decreased but still higher than the normal level，AQP4 expression also reached the peak at 48 h；the BBB permeability of brain tissue around the infarcted area was significantly positively correlated with the change of AQP4 expression （r=0.898，P<0.001）. Conclusion　Adenosine preconditioning can improve the permeability of blood-brain barrier and protect the brain，which may be achieved by reducing the expression of AQP4 protein.