Aim To study the effect of asiaticoside on the inflammatory response in the aneurysm wall of rats with cerebral aneurysm by down-regulating TLR9/MyD88/NF-κB p65. Methods The CA rat model was established, they were randomly divided into model group, asiaticoside (50 mg/kg) group, CpG-ODN (TLR9 activator, 4 mg/kg) group, asiaticoside (50 mg/kg) + CpG-ODN (4 mg/kg) group, with 12 rats in each group, another 12 rats were set as sham operation group. After group treatment, the thickness of the cerebral vessel wall and the volume of the aneurysm in the rats were measured, the morphology of cerebrovascular tissue was detected by HE staining, the levels of IL-1β and TNF-α in rat brain blood vessels and serum were detected by enzyme-linked immunosorbent assay (ELISA), the protein levels of TLR9, MyD88, and nuclear NF-κB p65 in rat brain vascular tissues were detected by Western blot. ResultsCompared with the sham operation group, the vascular wall became thicker, the cerebral arteries bulged and showed tumor-like changes and other CA symptoms, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the model group (P＜0.05). Compared with the model group, the symptoms of CA became lighter, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level decreased significantly in the asiaticoside group (P＜0.05); but the symptoms of CA were aggravated, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the CpG-ODN group (P＜0.05). Compared with the asiaticoside group, the symptoms of CA were aggravated, the brain blood vessel wall thickness, aneurysm volume, cerebrovascular tissue and serum IL-1β and TNF-α levels, cerebrovascular tissue TLR9, MyD88 levels and nuclear NF-κB p65 protein level increased significantly in the asiaticoside+CpG-ODN group (P＜0.05). Conclusion Asiaticoside can reduce the inflammation of the cerebral artery tissue of CA rats and reduce the tumor size by down-regulating the expression of TLR9/MyD88/NF-κB p65 pathway protein.