Abstract: OBJECTIVE To study the effect of butylphthalide(NBP) on the inflammatory response of human brain microvascular endothelial cells(HBMEC) under the condition of glucose and oxygen deprivation(OGD). METHODS HBMEC cells were treated by OGD. The cells were divided into control group, model group, low, middle high dose of NBP group. The control group was normal cultured, the model group were OGD treated, the low dose group was OGD+5 mol·L^-1 NBP, the middle dose group was OGD+10 mol·L^-1 NBP, and the high dose group was OGD+20 mol·L^-1 NBP. The cell apoptosis was detected by flow cytometry. The changes of cell vitality were detected by CCK-8. The expression of HMGB1, TLR4, NF-κB (p-P65), caspase-1 and procaspase-1 were detected by Western-Blot. The secretion level of interleukin 1β(IL-1β), tumor necrosis factor α(TNF-α) and interleukin 6(IL-6) in supernatant were detected by immunoenzyme linked immunosorbent assay. The mRNA expression of HMGB1, TLR4, NF-κB(P65), Caspase-1 and IL-1β were detected by real time fluorescence quantitative PCR. RESULTS OGD treatment could induce HBMEC activity and apoptosis of HBMEC to be down regulated and time-dependent, which was significantly different from that of the control group(P<0.05). After NBP treatment, the activity of HBMEC was significantly higher than that of the model group(P<0.05), and the apoptotic rate was decreased significantly compared with the model group(P<0.05). OGD treatment could lead to the activation of HMGB1-TLR4-NF-κB signal in HBMEC, and the expression of inflammatory factors caspase-1 and IL-1β was up-regulated. Compared with the control group, there was a significant difference(P<0.05). NBP could reduce the expression of HMGB1-TLR4-NF-NF-κB signal and down regulate the expression of caspase-1 and IL-1β. CONCLUSION NBP may regulate the inflammatory response of HBMEC cells under OGD by inhibiting the expression of HMGB1-TLR4-NF-κB signaling.