Objective To observe the expression of neuron specific enolase (NEC) to evaluate the neuroprotective effect of a cell-penetrating Bax-inhibiting peptide (BIP) on neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods Wi-star rats (7-day old) were randomly divided into Sham group, BIP group and HIBD group. After modeling HIBD, the histologi-cal (HE staining) and immunohistochemistry methods were used to determine the apoptotic pathological changes and the NSE expression levels in the brain at different time points. Results Compared to the Sham group, the rats of HIBD group showed significant apoptotic pathological changes. The histological changes and the brain damages were improved significantly in BIP group at each sampling point. The number of NSE-positive cells was significantly decreased in HIBD and BIP groups over time (P<0.05). The number of NSE-positive cells had significant difference among different groups at 48 h, 96 h and 7 d after opera-tion (F=45.35-81.66, P<0.01). The number of NSE-positive cells in the HIBD group was smaller than that of the Sham group and BIP group 48 h after operation (P<0.05). The number of NSE-positive cells in the BIP group was smaller than that of the Sham group 96 h after operation (P<0. 05). Conclusions BIP can decrease the apoptosis of cortex nerve cells in 7-day old HIBD rat model, and may have neuroprotective effect on the early stage of HIBD.