Abstract: Objective To investigate the effect of periodontal therapy in controlling periodontitis and on insulin resistance and lipid metabolism in obese rats with periodontitis. Methods Sprague-Dawley rats were randomized into normal group (group C), obese group (group O), periodontitis combined with obesity group (group P) and periodontal treatment group (group T). The obese rats in groups P and T were subjected to ligation of the maxillary second molar with silk thread to induce experimental periodontitis, and the rats in group T received periodontal therapy after the ligation. All the rats were sacrificed at the age of 24 weeks for measurement of blood lipids, insulin and blood glucose levels, and insulin resistance index (HOMA-IR) was calculated. The expressions of insulin receptor substrate-1 (IRS-1) and IRS-2 in the liver tissues were detected using real-time quantitative polymerase chain reaction (RT-PCR). Results Compared with the obese rats in group O, the rats in group P showed significantly higher HOMA-IR and LDL-C and lower expressions of IRS-1 and IRS-2 mRNA expression and HDL-C level (P<0.05). Compared with those in group P, the mRNA expressions of IRS-1 and IRS-2 and HDL-C level were significantly increased and LDL-C level, TC level and HOMA-IR were all decreased in group T (P<0.05), but the level of TG was comparable between the two groups. Pathological examination revealed lessened inflammatory cell infiltration and tissue destruction in the upper jaw of the rats in group T; the rats in group P presented with the most obvious upper jaw destruction and steatosis and inflammatory cell infiltration in the liver. Conclusion Periodontal inflammation can downregulate the expression of IRS-1 and IRS-2 and increase insulin resistance and dyslipidemia in obese rats. Periodontal therapy produces a beneficial effect in improving insulin resistance and reducing dyslipidemia in obese rats.