Abstract： Objective To study the relationship between the expression of aquaporin-4(AQP-4) and hypoxic-ischemic brain damage (HIBD) in neonatal rats. Metheods Totally 120 seven-day-old Wistar rats were assigned to four parts, each part (n=30) was divided into six groups, including control group, HIBD 6 h,24 h,3 d,5 d,7 d(n=5 per group ). The model of HIBD was induced by unilateral carotid ligation followed by exposure to 8% oxygen. In situ hybridization and immunohistochemistry were respectively used to evaluate AQP-4 mRNA and protein expression, and the light microscopic changes were observed by HE staining.Results The brain water content was increased markedly in HIBD group after 6 h,24 h, 3 d of HIBD and increased further with time in neonatal rats compared with that in the control group. The expression levels of AQP-4 mRNA and protein were low in the control group. Compared with the control group, there showed significant increase in AQP-4 mRNA and protein expression on the cerebral tissue at the 6th and 24th hour in rats following HIBD. AQP-4 mRNA expression(A Value) increased from 0.42±0.04 to 0.80±0. 02 (P＜0. 05) and AQP-4 protein expression (A) increased from 0.14±0.03 to 0.23±0.05. Histological study showed that the cerebral tissue had a light swelling. At day 3, the expression levels of AQP-4 mRNA and protein reached at its maximum. AQP-4 mRNA expression(A) reached at 0.91±0.08 and AQP-4 protein expression(A) at 0.41±0. 04 (P＜0.05 ). The brain edema became remarkable, neurons and glias together with endothelial cells were all remarkably swelling. At day 5 and 7, the expression levels of AQP-4 mRNA and protein in HIBD group were still higher than those in the control group(P＜0.05), and the brain edema were not remarkable. The AQP-4 mRNA expression showed a positive correlation with the AQP-4 protein expression during the HIBD formation (rs＞0. 82, Ps＜0.05 ). Conclusions The increased expression of AQP-4 participates in the development of cerebral edema after HIBD. AQP-4 may play an important role in the pathological development of HIBD.