The present study aimed to investigate whether inflammation-associated responses in piglets are induced by high protein (HP) through activating nuclear factor kappa B (NF-κB) signaling.Sixteen piglets(35 d of age,Duroc ×[Landrace × Yorkshire],weaned at d 21,initial BW =9.70 ± 0.11 kg) were allocated to 18% and 26% CP (HP group) at random,comprising 8 replicate pens per treatment.The piglets were slaughtered to collect intestinal tissues when apparent,persistent,and stable diarrhea syndromes happened (on d 12).No significant differences were observed in their growth performance (P > 0.05),but reduction by 19.11%,25.31%,23.64% ofADFI,ADG,and G:F,respectively was detected in the HP group.The HP group had greater (P =0.002) diarrhea rates.Furthermore,dietary HP had lower ileal villus height(VH;P =0.048),ratio of villus height to crypt depth (VH/CD ratio;P =0.016),and colonic CD (P =0.034),as well as had the trend (P =0.075) to reduce the ileal villus absorptive area.Moreover,HP diets significantly elevated the goblet cell numbers in the ileal villi (P =0.016) and colonic crypts (P < 0.001)and up-regulated (P =0.012) the mRNA expression of mucin2 (Muc2) in the ileum.In addition,HP diets increased the myeloperoxidase concentration in the ileum (P =0.002) and colon (P =0.007) of piglets.Dietary HP significantly down-regulated the mRNA expression of tumor necrosis factor-α (TNF-α;P < 0.001) in the ileum,induced nitric oxide synthase (iNOS;P =0.040) and interleukin-22 (IL-22;P =0.008) in the colon,and inclined to down-regulate interleukin-1β (IL-1β;P =0.076) expression in the colon.The relative protein abundance of Galectin-3 (P =0.046) in the colon and the ratio of phos-phorylation NF-κB to NF-κB (p-NF-κB/NF-κB ratio) in the ileum of HP piglets were also greater(P =0.038).These results suggest that dietary HP may cause diarrhea in piglets by activating NF-κB signaling induced intestinal inflammation.