Aim To investigate the effect of Songling Xuemaikang (SX) on vascular endothelial function and its protective mechanism in rats with cerebral atherosclerosis (CAS). Methods SD rats were divided into 3 groups:control group, CAS group and the SX group. CAS model of hypertension and hyperlipidemia was established in the CAS group and the SX group. Rats in the SX group were treated by Songling Xuemaikang. The blood pressure and blood lipid indexes of each group of rats were detected and compared. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of basilar artery and brain tissue. Serum levels of nitric oxide (NO) and endothelin-1 (ET-1) were measured by enzyme-linked immunosorbent assay. The expression levels of Notch1 and Hes1 protein were detected by Western blot. Results The blood pressure and blood lipid levels of the CAS group were significantly higher than those of the control group (P＜0.05). The blood pressure and blood lipid levels of the SX group were significantly lower than those of the CAS group (P＜0.05). The basilar artery morphology of the control group was normal. In the CAS group, the intima of the rat was damaged, the lipid was deposited in the intima of the artery, and the smooth muscle cells in the middle layer of the artery were disordered. The pathological morphology of the SX group was between the control group and the CAS group. The NO of the CAS group was significantly lower than that of the control group and the ET-1 was significantly higher than the control group (P＜0.05). The NO of the SX group was significantly higher than that of the CAS group and the ET-1 was significantly lower than the CAS group (P＜0.05). In the control group, the brain tissue structure was completed, the cells were normal, the nucleolus was obvious, and the cytoplasm was abundant. In the CAS group, the brain cells of the rats were arranged one time, the nucleoli were not obvious, and the cytoplasm showed empty halos. The morphology and arrangement of the SX group were basically normal, and the nucleolus and cytoplasm were clear. The levels of Notch1 and Hes1 in the CAS group were significantly higher than those in the control group (P＜0.05). The levels of Notch1 and Hes1 in the SX group were significantly lower than those in the CAS group (P＜0.05).Conclusion Songling Xuemaikang has the effect of protecting vascular endothelial cells caused by hypertension and hyperlipidemia and antagonizing brain damage, which may be related to the inhibition of Notch pathway.