OBJECTIVE: To explore the role of Caspase-3 protein and DNA fragmentation at late stage after hypoxic ischemic brain damage (HIBD) and the effect of basic fibroblast growth factor (bFGF) on Caspase-3 expression. METHODS: Seven day old Wistar rats were randomly assigned into HIBD group, sham operated group, normal saline treatment group and bFGF treatment group. Caspase-3 expression of the brain was measured by the immunohistochemical method and DNA fragmentation of neurocytes was detected by TUNEL at 2 w, 3 w or 4 w after hypoxia ischemia (HI). RESULTS: ① The number of the TUNEL positive cell in the HIBD group at 2 w and 3 w after HI was greater than that of the sham operated group (P< 0.05 ). ② The Caspase-3 average OD values of the brain ( 0.39 ± 0.04 , 0.38 ± 0.04 ) in the HIBD group at 2 w and 3 w after treatment were significantly higher than those in the sham operated group ( 0.36 ± 0.01 , 0.36 ± 0.02 ), P< 0.05 . ③The Caspase-3 average OD value in the bFGF group at 3 w after HI ( 0.36 ± 0.09 ) was significantly lower than those in the control group and HIBD group ( 0.37 ± 0.04 , 0.38 ± 0.04 ), P< 0.05 . ④ The number of the TUNEL positive cell in the bFGF group at 3 w after treatment ( 4.20 ± 1.30 ) was significantly less than those in the control group and HIBD group ( 9.80 ± 1.92 , 8.00 ± 1.00 ), P< 0.05 . CONCLUSIONS: Caspase-3 may take part in the pathogenesis of HIBD and keep continuous activation, suggesting a prolonged role for apoptosis in neonatal HIBD. bFGF has neuroprotective effects against neonatal HIBD by down regulating Caspase-3 protein expression and preventing DNA from fragmentation.