ObjectiveTo ascertain the role of inducible nitric oxide synthase (iNOS) in the periodontitis response during diabetes. MethodsTwenty-four male SD rats were randomly divided into four groups: control group (Control), diabetes mellitus group (D), diabetes mellitus plus periodontitis group (DP), and periodontitis group (P). Periodontitis and diabetes were established separately. Then the gingival tissue and alveolar bone were collected. A stereomicroscope was used to evaluate bone loss. The expression of iNOS, TNF-α, and NF-κB in the gingiva was detected by immunohistochemical staining, real-time PCR, and western blot analysis. ResultsSignificant bone loss was observed in the DP and P groups and more extensive bone resorption was discovered in the DP group than in the P group (P < 0.05). The immunohistochemical staining analysis revealed enhanced expression of iNOS located in the gingiva of the three disease groups compared with the control group (P < 0.05). In particular, the level of iNOS was significantly higher in the DP group than in the P group (P < 0.05). This elevated trend of iNOS was further demonstrated by quantitative PCR and western blot analysis. Similarly, the mRNA and protein expression levels of NF-κB in the D, DP, and P groups were significantly higher than those of the control group, as was the level of TNF-α protein (P < 0.05). ConclusionsOur results proved diabetes exacerbated alveolar bone resorption in a periodontitis rat model. iNOS may be the inflammatory mediator in the course of periodontal injury promoted by diabetes.