Objective To investigate the influence of Tanshinone Ⅱ A on the expression of HMGB1 in rats with cerebral ischemia-reperfusion (I/R) injury and its neural function protection.Methods The 32 male SD rats were randomly (random number) divided into 4 groups (8 rats per group):Sham group,I/R group,group with low dose of Tanshinone Ⅱ A ( TaLD group) and group with high dose of Tanshinone Ⅱ A (TaHD group).The cerebral I/R models were established by the method of right middle cerebral artery occlusion (MCAO).Cerebral infarct volume was detected by TTC staining.Apoptotic cell and apoptotic index were calculated by Tunnel assay.The HMGB1 levels in brain and serum was detected by Western blot and ELISA.Calmodulin (CaM) activity and malondialdehyde (malondiadehyde,MDA) content in the brain were also detected.Results Compared with the Sham group,the volume of cerebral infarction,the number of apoptotic cells,CaM activity,MDA content,HMGB1 levels in the brain tissue and serum in group I/R,TaLD group and TaHD group increased significantly (P ＜ 0.01 ).Compared with the group I/R,the volume of cerebral infarction,the number of apoptotic cells,CaM activity,MDA content and the HMGB1 levels in brain tissue and serum in TaLD groupand TaHDgroup decreased significantly (P ＜ 0.01 ).The difference of the above index between TaLD groupand TaHDgroup was significant ( P ＜ 0.01 ).Conclusions Tan Ⅱ A could reduce the cerebral ischemic reperfusion injury in rats which was likely related with decreasing the inflammatory response in the late stage via HMGB1.