The purpose of this study was to assess the impact of supplementing broiler diets with Artemisia ordosica aqueous extract (AOE) on small intestine inflammation and the expression of antioxidant-related genes in broilers subjected to lipopolysaccharide (LPS) challenge. A total of 96 one-day-old Arbor Acres broilers (half males and half females, with an initial body weight of 50 ± 4.5 g) were assigned into four treatment groups. These groups included broilers fed a basal diet (control), broilers fed a diet containing 1000 mg/kg AOE, broilers on a basal diet subjected to LPS challenge, and broilers on a diet with 1000 mg/kg AOE subjected to LPS challenge. Each treatment consisted of six replicates, with four chicks per replicate. On days 14, 16, 18 and 20, broilers were injected with LPS or an equivalent amount of saline. The results demonstrated that dietary AOE significantly decreased the expression of inflammationrelated genes in the small intestine of broilers challenged with LPS. Specifically, there were significant reductions (P < 0.05) in the levels of toll like receptor 4 (TLR4), lipopolysaccharide-induced TNF factor (LITAF) and nitric oxide synthase 2 (NOS2) in the duodenum, TLR4, nuclear apoptosis-inducing factor 1 (NAIF1), interleukin (IL)-1B, IL-6, LITAF and NOS2 in the jejunum, and RELA proto-oncogene nuclear factor kappa B (NF-κB) subunit, IL-1B and NOS2 in the ileum. Moreover, catalase gene expression was increased in the duodenum and jejunum, while glutathione peroxidase was upregulated in the ileum (P < 0.05) of LPS-challenged broilers. In conclusion, dietary AOE supplementation could partly alleviate the adverse effects induced by LPS by improving the expression of genes encoding antioxidant enzymes and reducing the expression of inflammation-related genes in the small intestine of broilers.