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This study was conducted to evaluate the intestinal protective effects of baicalin (BAI) in deoxynivalenol (DON)-treated piglets. A total of 320 weaned piglets were randomly allotted to 1 of 4 treatments with 8 replication pens per treatment and 10 piglets per pen. The treatments were basal diet (NC), basal diet + 0.1% baicalin (BAI), basal diet + 4 mg/kg DON (DON), and basal diet + 4 mg/kg DON + 0.1% BAI (DON + BAI). The experiment was conducted for 14 days. BAI supplementation alleviated the impairment of growth performance and the disorder of serum biochemical parameters in DON-challenged piglets. BAI supplementation also alleviated DON-induced negative effects, decreasing protein and gene expression levels of pro-inflammatory cytokines in the serum and intestinal tissue and increasing antioxidant capacity in the serum. BAI increased villus height and villus height/crypt depth but decreased the protein expression levels of nuclear factor kappa B (NF-κB), as determined by immunohistochemical analysis, in the ileum and jejunum. Moreover, we found that BAI inhibited NF-κB and increased mTOR protein and gene expression levels in the serum and intestinal tissues. Collectively, BAI alleviates intestinal inflammatory and oxidative damage by inhibiting NF-κB and increasing mTOR signaling to modulate downstream inflammatory and oxidative responses after DON challenge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)