Abstract: Objective To investigate the protective effect of SHH signaling pathway on middle cerebral artery occlusion (MCAO) model rats after cerebral ischemia. Methods Total 30 SD rats were randomly divided into three groups:sham operation group, model group and SHH group, 10 rats each groups. The MCAO model was made by the modified longa suture method. In the SHH group, 2 μL (1 μg/μL) SHH protein was injected into the left lateral ventricle, and the same amount of PBS solution was injected into the sham operation group and the model group. Results The neurological function scores of the SHH group were lower than those of the model group at 3 days (1.23±0.16 vs. 2.10±0.25) and 7 days (0.87±0.13 vs. 2.38±0.19) after operation (t=9.269, 20.741, all P<0.05). The infarct volume of the SHH group were lower than those of the model group at 3 days (32.14±7.25 vs. 60.27±5.64) and 7 days (21.98±4.56 vs. 64.82±7.19) after operation (t=9.684, 15.912, all P<0.05. The value of cerebral blood flow in the SHH group were higher than that in the model group at 3 days[(348.92±29.38) PU vs. (163.28±26.13) PU] and 7 days[(413.24±56.29) PU vs. (130.29±23.42) PU] after operation (t=14.930, 14.676, all P<0.05). The CDK2 (27.18±3.10) and CyclinD1 (24.52±4.31) in the SHH group were lower than those in the model operation group (59.83±5.62 and 67.38±7.39), t=16.087, 15.843, all P<0.05. Conclusion SHH signaling pathway can reduce the neurological damage of cerebral infarction in MCAO model rats after cerebral ischemia, it can regulate the expression of CDK2 and CyclinD1 to achieve the neuroprotective effect.