Objective To observe the effects of velcade on inflammatory reaction and cell apoptosis after ischemia-reperfusion injury, and to explore the neuroprotective mechanism of velcade.Methods The 15 male Wistar rats were randomly divided into sham-operated group, physiological saline control group and velcade-treated group (n= 5, each). The model of temporary middle cerebral artery occlusion (MCAO) was applied and reperfused after 2 hours. Immediately after the reperfusion, all rats were performed intraperitoneal injection with velcade 0. 2 mg/kg in velcadetreated group, and with the same volume of physiological saline in control group. After 24 hours, the rats were decapitated in all groups. The apoptosis cells were found by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the expressions of nuclear factor-κBp65 (NF-κBp65) and interleukinh-1β (IL-1β) were detected by immunohistochemistry. Results The immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were occasionally found in shamoperated group [(1.21 ± 0. 16)/400 power, (11.56 ± 0. 99)/400 power and (2. 88 ± 0. 27)/400 power], while a lot of immunologically positive cells of NF-κBp65, IL-1β and apoptosis cells were found in velcade-treated group and control group. The control with compared group, these cells were significantly more in the velcade-treated group [(56.28± 1.95)/400 power vs. (29. 76±2.53)/400 power, (47. 64±2.06)/400 power vs. (29.6±1. 61)/400 power and (51. 05±4. 23)/400 power vs.(33.44±2.06)/400 power, all P＜0. 05]. Conclusions The velcade could decrease the expressions of the NF-κBp65 and IL-1β and diminish the neuronal apoptosis. The neuroprotective mechanism of velcade may lie in decreasing apoptosis through inhibiting inflammation.