Abstract: Abstract: Objective To investigate the expression of high mobility group box-1 protein (HMGB1) and its downstream products, receptor for advanced glycation end-products (RAGE) and tumor necrosis factor⁃α (TNF⁃α), in periodontal tissues of diabetic rats with periodontitis, and explore the association of HMGB1 with hepatic lipid metabolism. Methods Immunohistochemical staining was used to detect the expression of HMGB1, RAGE and TNF-α in the periodontal tissues in rat models of diabetes mellitus (DM), periodontitis (CP), and diabetic periodontitis (DM + CP). The serum levels of the indicators of lipid metabolism and biochemical indexes of liver damage were detected by spectroscopy. Results The expressions of HMGB1 and RAGE in the periodontal tissues were significantly higher in DM group than in the control group,but the expression of TNF-α showed no significant difference among the groups. In CP group, the expressions of HMGB1 and TNF-α were significantly higher than those in the control group, and the expression of RAGE was comparable with that in the control group but significantly lower than that in DM and DM+CP group. The expressions of HMGB1, RAGE and TNF-α were all significantly higher in DM+CP group than in the control group. Compared with the control rats, the rats in DM, CP, DM+CP group all showed abnormal hepatic lipid metabolism with significantly elevated serum ALT levels. Conclusion HMGB1 and RAGE participate in the inflammation of the periodontal tissues in diabetic rats. Diabetes leads to elevated expression of HMGB1 in the periodontal tissues. Both periodontitis and hyperglycemia contribute to liver metabolic dysfunction. HMGB1-RAGE provides clues in the study of signaling pathways underlying the mutual susceptibility of diabetes and periodontitis.