Objective:Chinese rhubarb,one of general traditional Chinese herbal medicine,has been widely used for protecting gastrointestinal mucous and controlling the SIRS damage.However,the effect of Rhubarb on lipopolysaccharide(LPS)-induced sepsis has not yet been reported.This research aims to detect the effect of Rhubarb on LPS-induced sepsis in rat,and to investigate the molecular mechanisms.Methods: Rhubarb extract was given by intragastric administration twice a day for 7 days,and rats were sacrificed at 4h and 6h after LPS injection.The ELISA technique was used to examine the production of inflammatory cytokines IL-6,IL-1β,and TNF-α; and Western blot and real time RT-PCR were used to determine the effect of Rhubarb on TLR4,ERK,JNK,IκBα and NF-κB p65 proteins and gene expression.Results: The results indicated that Rhubarb treatment markedly attenuated the damage of the sepsis induced by LPS,suppressed the levels of IL-6,L-1β,TNF-α and NO/iNOS in LPS-induced rats.Besides,rhubarb down-regulated the expression of Toll-like receptor 4(TLR4)and then inhibited the phosphorylation of ERK,JNK and p38 in mitogen-activated protein kinase(MAPK)signal pathway and suppressed the phosphorylation of IκBα and NF-κB p6.Conclusions: According to Multivariate Analysis of Variance and Principal Component Analysis,we can conclude that Rhubarb extract could regulate the TLR4-MAPK-NFκB signaling pathways,and the key targets were Erk,JNK,IκBα,NF-κB p65 in the middle signal pathway.