Abstract: Objective To explore the effects of soy isoflavone (SIF) on low-grade inflammation in rats with high-fat diet-induced insulin resistance (IR) and explore the mechanisms of SIF in improving insulin sensitivity. Methods The rats with high-fat diet-induced IR were randomly divided into one model control group and 3 SIF groups gavaged with SIF water solutions at the doses of 50, 150, and 450 mg/kg, respectively. One month after the treatment, fasting blood glucose (FBG), fasting insulin (FINS), interleukin-6 (IL-6), tumor necrosis factor- α(TNF-α), C-reactive protein (CRP), resistin and adiponectin in the serum were detected by enzymatic method, radioimmunoassay, or enzyme-linked immunosorbent assay. Results In the 150 and 450 mg/kg SIF groups, fasting body-weights, visceral adipose tissue deposition, FINS, resistin, TNF-α in serum, and IR index were lowered in comparison with the model control group, and in 450 mg/kg SIF group, serum IL-6 level was obviously lowered, and adiponectin increased. No differences were found in serum C-reactive protein levels between the 3 SIF groups. Conclusion Soy isoflavone may ameliorate insulin sensitivity by decreasing visceral adipose deposition and adjusting low-grade inflammatory molecules derived from white adipose tissue.