In the present study, we found for the first time that RAGE-aptamer significantly inhibited the binding of HMGB1 to vRAGE in vitro and that intraperitoneal administration of 40 pmol/g-BW RAGE-aptamer improved the sepsis score measured at 8 hours after LPS injection and survival rate in LPS-injected septic mice. This evidence concerns the gene HMGB1 and Sepsis.