[Abstract ] Objective The purpose of this study was to observe the effects of dl-3n-butylphthalide (NBP) sodium chloride injection post-processing on the expressions of X-inhibitor of apoptosis (XIAP) and Bcl-2/adenovirus E1B19kDa interacting protein 3 (BNIP3) in the hippocampus CA1 neurons of focal cerebral ischemia reperfusion (IR) rats, and to investigate the brain-protection mechanisms of NBP. Methods A total of65 adult male Sprague-Dawley rats were divided into five groups of equal number, sham op-eration, IR, and low-,medium -and high-dose NBP, according to the random number table. The IR models were established by modified ligation of the middle cerebral artery.The animals in the NBP groups received intra-abdominal injection of NBP at 2, 4, and 6 mg/kg, re-spectively.All the rats were sacrificed at 24 hours after modeling,neurological scores obtained by Zea Longa, the volume of infarction measured by TTC staining, the number of apoptotic cells counted by TUNEL, and the expressions of XIAP and BNIP3 detected by immunohistochemistry and real-time PCR. Results The neural function defect scores were markedly lower in low-, medium-and high-dose NBP groups than in IR model rats (P<0.05), with statis-tically significant differences among the three dose groups (P<0.05).The volume of infarction was remarkably higher in the low-dose than in the medium-and high-dose NBP groups (P<0.05).The number of apoptotic cells in the hippocampus CA1 neurons was de-creased in the NBP groups as compared with the IR models (P<0.05).The XIAP-and BNIP3-positive cells were significantly in-creased in the IR model rats as compared with the sham operation group ([22.31 ±0.94] and [60.13 ±2.59]/HP vs [3.07 ±1.43] and [5.78 ±0.44]/HP, P<0.05).In comparison with the IR models, the NBP-treated rats showed a progressively increased number of XIAP-positive cells in low-, medium-, and high-dose groups ([28.70 ±1.18], [32.79 ±0.88], and [37.01 ±1.24]/HP) (P<0.05) but a decreased number of BNIP3-positive cells in the three dose groups ([52.07 ±1.02], [40.30 ±2.00], and [31.04 ± 0.43]/HP) (P<0.05).Similarly, the expression of XIAP mRNA was up-regulated while that of BNIP3 mRNA down-regulated in the NBP treatment groups as compared with the IR model rats, both in a dose-dependent manner (P<0.05). Conclusion NBP post-processing has a neuroprotective effect on IR rats, which is associated with its impact on the expressions of XIAP and BNIP3.