Objective To investigate the role of IL-6/STAT3/miR-21 in the treatment of cerebral ischemia reperfusion injury in mice by pine bark extract.Methods 120 KM mice were randomly divided into normal control group,sham operation group,14 d and 28 d model groups,14 d and 28 d treatment groups,each group with 20 mice.The model of cerebral ischemia-reperfusion injury model was made by bilateral common carotid artery occlusion.The mice in the treatment group were treated with pine bark extract procyanidins by intragastric administration for 7 days before the execution.The control group and sham operation group were treated with normal saline.The differences in learning and memory abilities and histopathological changes in the hippocampus of mice in each group were examined.The levels of interleukin 6,STAT3,p-STAT3 and miR-21 were measured.Results The learning and memory abilities of the mice in the treatment group were higher than that in the model group at the same time points.The treatment group had less irregularity in the arrangement of Nissl body,irregular shape of the cells,with relatively lighter cytoplasmic staining,but was better than the model group.The expression level of IL-6 in the 28 d model group was lower than that in the 14 d model group,The IL-6 in the hippocampus of the treatment group was significantly lower than that in the model group at the same time point.There were no significant differences in the contents of total STAT3 protein in the hippocampus between the groups (P>0.05).The expression of p-STAT3 in the treatment group was lower than model group at the same time point.The expression of miR-21 in the hippocampus of 14 d,28 d treatment groups was lower than that in the model group at the same time point,and decreased with time.Conclusions The procyanidins extracted from pine bark may effectively inhibit IL-6,then the phosphorylation level of STAT3 is significantly decreased and finally decreases the expression of miR-21,so as to alleviate the cerebral ischemia reperfusion injury in mice.