AIM: To investigate the role of tri-iodothyronine supplement in protecting gut barrier in septic rats. METHODS: Twenty-two rats were randomized into three groups: sham group (n=6), sepsis group (n=8), and sepsis plus tri-iodothyronine (T3) group (n=8). Septic rat model was established through cecal ligation and puncture (CLP). After 5 h, sham and sepsis groups received saline, and the remaining group received T3 intraperitoneally. Twenty-one hrs After CLP, intestinal permeability and serum free T3 and T4 were measured with fluorescence spectrophotometer and by radioimmunoassay, respectively. Intestinal ultrastructure and histologic morphology were observed under transmission electron microscopy (TEM) and light microscopy, respectively. RESULTS: After 21 h, septic symptoms and signs in sepsis plus T3 group were milder than those in sepsis group. Serum FT3 or FT4 concentration in sepsis group was lower than that in sham group (1.59