Introduction: The incidence of obesity has dramatically increased worldwide. Obesity has been shown to exacerbate the progression of periodontal disease. Studies suggest a sex difference in periodontitis, whereby males are more sensitive to periodontal inflammation compared to females. Aim: In the current study, it was hypothesized that obesity drives periodontal inflammation and bone loss in both sexes. Methodology: Utilizing leptin receptor mutant (SSLepR mutant) rats as a genetic model of obesity, 11–12-week-old male and female lean Dahl salt-sensitive (SS) rats and obese SSLepR mutant rats were used to investigate sex differences in obesity-induced periodontal inflammation. Results: Body weight, insulin, hemoglobin A1c and cholesterol levels were significantly elevated in the obese SSLepR mutant strain vs. the lean SS strain within the same sex. Sex differences in body weight and plasma hemoglobin A1c were only observed in obese SSLepR mutant rats, with males having significantly greater body weight and hemoglobin A1c vs. females. Plasma thiobarbituric acid reactive substances (TBARs) and monocyte chemoattractant protein-1 (MCP-1), markers of systemic oxidative stress and inflammation, respectively, were significantly elevated in obese SSLepR mutant rats vs. lean SS rats, with no sex differences in these parameters in either rat strains. Although micro-CT analyses of the maxillary first molar alveolar bone from obese SSLepR mutant rats revealed no evidence of bone loss and/or sex differences, immuno-histochemical analysis revealed significant elevations in periodontal IL-6 and decreases in IL-10 in obese SSLepR mutant rats vs. lean SS rats, with no apparent sex differences in these parameters. Conclusions: Obesity increases systemic and periodontal inflammation, without evidence of bone loss or apparent sex differences in SSLepR mutant rats.