Abstract: Objective To investigate the effects of Huoxue Lishui Recipe on the expression of EGFR and AKT protein and mRNA in hippocampus of middle cerebral artery occlusion (MCAO) model of rats. Methods Sixty-four rats were divided into normal group n=16,10 ml/(kg·d) distilled water,model group n=16,10 ml/(kg·d) distilled water,Ginaton group n=16,100 mg/(kg·d)Ginaton and Huoxue Lishui Recipe group n=16,15 g/(kg·d) Huoxue Lishui Recipe.After MCAO model was established by suture method for 24h,3 rats in each group were sacrificed,and their brain tissues were identified by chlorotriphenyltetrazolium (TTC) staining.At 1 d,7 d,and 13 d,corner turning test,balance beam experiment,and Morris water maze test were used to detect behavioral changes.At 14 day,all the rats were sacrificed to obtain the ischemic hippocampus.The expression of EGFR and AKT protein and mRNA were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Results TTC staining indicated that MCAO model was successful established in each group.Corner turning test results showed that there were a significant differences between the Huoxue Lishui group and the model group at the 7 d and 13 d 7 d:(81.16±3.43)% vs (89.51±4.41)%;13 d:(63.81±5.05)% vs (74.50±6.31)%;P<0.05,respectively;Compared to baseline,corner turning test scores in the model group,the Ginaton group and the Huoxue Lishui group increased significantly at 7 d and 13 d (P<0.05).Balance beam experiment results showed that the Ginaton group and the Huoxue Lishui group had significantly higher scores compared with the model group at 7 d (4.68±0.70) and (4.37±1.15) vs (3.43±0.63),P<0.05,respectively and at 13 d (5.23±0.58) and (5.45±0.51) vs (4.32±0.70),P< 0.05,respectively;Compared with baseline,the balance test score increased significantly in the model group,the Ginaton group and the Huoxue Lishui group at 7 d and 13 d (P<0.05).Morris water maze test results showed at 13 day,there was a significant difference between the model group and the Huoxue Lishui group (47.96±5.93) seconds vs (54.62±4.47) seconds,P<0.05;compared with baseline,the latency increased significantly in each group at 7 d and 13 d (P<0.05).Western Blot test indicated the expression of EGFR protein in the Huoxue Lishui group was significantly higher than that of the model group (0.83±0.07 vs 0.62±0.12,P<0.05);The results of RT-PCR also showed that the expression of AKT mRNA in the Huoxue Lishui group was significantly higher (0.93±0.13 vs 0.51±0.11,P<0.05),so did the EGFR mRNA (0.86±0.14 vs 0.59±0.08,P<0.05). Conclusion Huoxue Lishui Recipe may play a therapeutic role in ischemic stroke by up-regulating the expression of EGFR and AKT protein and mRNA.