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AIM: To investigate the role of tri-iodothyronine supplementin protecting gut barrier in septic rats.METHODS: Twenty-two rats were randomized into threegroups: sham group (n=6), sepsis group (n=8), and sepsisplus tri-iodothyronine (T3) group (n=8). Septic rat modelwas established through cecal ligation and puncture (CLP).After 5 h, sham and sepsis groups received saline, and theremaining group received T3 intraperitoneally. Twenty-onehrs After CLP, intestinal permeability and serum free T3 andT4 were measured with fluorescence spectrophotometer andby radioimmunoassay, respectively. Intestinal ultrastructureand histologic morphology were observed under transmissionelectron microscopy (TEM) and light microscopy, respectively.RESULTS: After 21 h, septic symptoms and signs in sepsisplus T3 group were milder than those in sepsis group. SerumFT3 or FT4 concentration in sepsis group was lower than thatin sham group (1.59±0.20, 3.41±2.14 pmol/L vs 3.44±1.40,9.53+3.39 pmol/L, P＜0.05), and FT3 concentration in sepsisplus T3 group (3.40±1.65 pmol/L, P＜0.05) was corrected.Portal concentration of fluorescein isothiocyanate-dextran(FITC-D) in sepsis group (2.51±0.56 mg/L) was higher thanthat in sham group (1.22±0.21 mg/L) (P＜0.01), and in sepsisplus T3group (1.68+0.38 mg/L) it was decreased significantly(P＜0.01). TEM and light microscopy showed that T3supplement preserved well ultrastructure and morphologyof intetinal mucosa in septic rats.CONCLUSION: Tri-iodothyronine supplement protects gutbarrier in septic rats.