Objective:To explore the mechanism of the chronic stress contribution to periodontitis. Method:Sprague-Dawley rats(2 months)were received chronic unpredicted mild stress(CUS)for eight weeks. Then,four weeks later,they were devided into susceptible(depressive)or unsusceptible(resistant)groups according to sucrose preference test. Total body and adrenal weights of rats were weighed weekly and at 8 week,respectively. The levels of plasma corticosterone and insulin,the total insulin receptor(IRS)and activity-dependent phosphorylated IRS in the periodontal tissues,and the mRNA expression of IL-1β and TNF-α in the periodontal tissues were detected by enzyme-linked immunosorbent assay(ELISA),Western blot and Real-time PCR,respectively. Results:After 4 weeks of CUS,59% of rats showed a decrease of sucrose preference indicating anhedonic or depressive-like behavior(CMSA). Compared with controls,all the stressed rats showed decreased weight after three weeks;after eight weeks,they also exhibted increased corticosterone and decreased insulin in plasma,decreased p-IRS and increased mRNA levels of IL-1β and TNF-α in the periodontal tissue. The depressive andresitant groups showed no significant differences in above measures. Conclusion:The stress itself,rather than stress-induced mood disorders,leads to HPA axis disorders,abnormality of insulin signal pathway,and increased expression of periodontal tissue inflammatory factor. These changes may serve as the mechanism in contibuting to stress susceptible periodontal disease.