Abstract: Rabbits were oral administrated with water extract of Artemisia argyi Levl. et Vant. (Artemisia argyi),subsequently the animals were injected with or without inactivated E. coli. After that,an indirect ELISA was used to detect the specific antibody induced by inactivated E. coli, and challenge test was conducted to assess the immune protection effect induced by inactivated E.coil. In addition,the innate immunity of rabbits against E. coli were measured by the methods of ELISA,blood routine,blood biochemistry,limulus amoebocyte lysate test with a chromogenic substrate,and RT-PCR. The results showed that the improved level of specific IgM, IgG (P<0.01), and the survival of rabbits challenged with E. coli were found in the animals administrated with Artemisia argyi for 7 days as compared to the control. More importantly, the supplement of Artemisia argyi alone clearly increased the total IgG, IgA (P<0.05),and the number of neutrophils(P<0.05), platelets(P<0.01) in blood, while along with the reduced viable cells of E. coli (P<0.05), LPS level (P<0.01),AST and ALT (P<0.05) were observed in blood of animals challenged with E. coli. Additionally,it was observed in the drug group that the mRNA expression of cytokines (TLR4, TNF-α, IL-1β, IRF7, IFN-β) which were correlated with the LPS-TLR4 signaling pathway and over-expressed after challenge with E. coli were significantly down-regulated (P<0.01 or P<0.05). Collectively,Artemisia argyi is an excellent immunopotentiator to increase rabbits resistance to E. coli, and has its potential clinical application value.