Artemisia argyi polysaccharide (AAP) is an important active component extracted from the leaves of A. argyi. Currently, the effects of AAP in mouse model of intestinal inflammation are unclear. At the same time, it is uncertain whether AAP affects the intestinal flora. The study aimed to explore the improvement effects of AAP on lipopolysaccharide (LPS)-treated mice. The changes of intestinal tissue was observed with hematoxylin-eosin (HE) staining, also the mRNA expression of the intestinal barrier-related junction proteins were detected. The intestinal oxidation indices and inflammatory factors were detected with ELISA method, the nuclear factor kappa B (NF-κB) signaling pathway expression was evaluated with Western blotting, and the contents of short-chain fatty acids (SCFAs) in the colon were determined. At the same time, the changes of AAP on intestinal flora were evaluated. The study have shown that AAP downregulated the expression of NF-κB inhibitor protein α (IκBα), improved intestinal stress state, and inhibited the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), and interleukin-1β (IL-1β) in intestinal tissues. The contents of SCFAs (acetic acid, propionic acid, butyric acid) in the colon were increased, the numbers and composition of intestinal flora were changed after AAP intervention. In conclusion: AAP alleviated intestinal inflammation and intestinal flora dysbiosis in LPS-treated mice, it may play a key role in maintaining the intestinal barrier by regulating intestinal flora.