OBJECTIVE： To study the protective effect of butylphthalide on the apoptosis of human umbilical vein endothelial cells （HUVECs） induced by Aβ1-42 and its mechanism. METHODS： HUVECs were divided into normal control group， Aβ1-42 group， TAK242 group （10 nmol/L）， DMSO group （1‰DMSO） and butylphthalide low-concentration， medium-concentration and high-concentration groups （40， 80， 160 μg/L）. Except for normal control group and DMSO group， other groups were given 50 μmol/L Aβ1-42 to culture HUVECs for 24 h. TAK242 group， DMSO group and butylphthalide low-concentration， medium-concentration and high-concentration groups were given relevant concentration of drugs for 30 min， with 3 holes for each concentration. The cell viability was determined by CCK-8 assay； cell apoptosis was observed by Hochest 33342/PI double staining； the cell apoptotic rate was detected by AnnexinⅤ-fluorescein isothiocyanate （FITC） flow cytometry； the protein expression of TLR-4 and COX-2 were determined by Western blot assay； the contents of IL-1 and TNF-α were detected by ELISA. RESULTS： Compared with normal control group， cell viability of HUVECs were decreased in Aβ1-42 group； while apoptotic rate， protein expression of TLR4 and COX-2， the contents of IL-1 and TNF-α were increased. Compared with Aβ1-42 group， cell viability of HUVECs were increased in TAK242 group and butylphthalide low-concentration， medium-concentration and high-concentration groups； while apoptotic rate， protein expression of TLR4 and COX-2， the contents of IL-1 and TNF-α were decreased， with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Butylphthalide can reduce HUVECs apoptosis induced by Aβ1-42， which may be related with inhibiting the expression of TLR4， COX-2 and inflammatory factors.