Abstract： Objective　To study the effect of hypoxia-ischemia on cysteinyl aspartate-specific proteinases (caspase-3) activity in cerebral tissue of neonatal rat and probe into its significance. Methods　To induce hypoxic-ischemic brain damage (HIBD), the left carotid artery of rats at day 7 was ligated and animals were exposed to 8% oxygen for 2 hours. 0.5,12,24,and 48 hours after HIBD, both ipsilateral and contralateral cerebral tissue were ditected and homogenized. caspase-3 activity was measured by cleavage of the colorimetric substrate DEVD-pNA. Results　Caspase-3 activity in ipsilateral cerebral tissue increased gradually after HIBD and peaked at 24 hours, and then decreased significantly at 48 hours（P<0.001）. There were no significant changes in caspase-3 activity in the contralateral tissue at all time points (P>0.05）. Conclusions　Significant activation of caspase-3 after cerebral hypoxia-ischemia strongly suggests that apoptosis is involved in HIBD. Application of caspase inhibitors or other anti-apoptotic agents may become a new therapeutics of HIBD.