Background. According to the Consensus 2010 of the International Liaison Committee on Resuscitation (ILCOR), children with moderate to severe hypoxic-ischemic encephalopathy (HIE) should receive brain hypothermic therapy (BHT) after successful resuscitation. Elevated high mobility group box 1 (HMGB1) in the blood at the early stage of brain ischemia-reperfusion injury has been suggested to be involved in the release of various inflammatory cytokines. Methods. In total, 21 neonates plasma HMGB1 concentration was measured. These neonates included 8 with HIE in whom BHT was indicated, 5 controls diagnosed as having HIE but who were not suitable candidates for BHT, and 8 normal controls. Results. The umbilical artery HMGB1 (UA-HMGB1) level before undergoing BHT significantly exceeded reference values. The UA-HMGB1 level in the BHT (−) group did not differ significantly from reference values, but was significantly increased 24 hours after birth. Repeated measure ANOVA showed a significant difference in time course changes between the BHT (+) and BHT (−) groups (P=0.0002). Conclusions. This study demonstrated hypothermic therapy to significantly decrease HMGB1. Furthermore, HMGB1 is a useful index of the inhibition of early stage inflammation.