Objective: To investigate the effects of nonsurgical periodontal therapy on the serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) and on the carotid artery in rats with chronic periodontitis (CP) and with or without hyperlipidemia (HL). Methods: A total of 29 Sprague-Dawley rats were randomly divided into two groups: group A (CP, n = 14) and B (CP + HL, n = 15), and subjected to the corresponding treatment. Groups A and B were further divided into groups A1/B1 (without periodontal interventions) and A2/B2 (with periodontal interventions). The serum IL-6 and hsCRP levels were evaluated before periodontal intervention and at 1, 3, 5, and 7 weeks after periodontal intervention. The rats were euthanised 8 weeks after the periodontal intervention and the histopathologic changes in the carotid artery were observed. Results: The serum hsCRP and serum IL-6 levels in groups A1 and B1 were elevated with time; they were significantly higher in group B1 than in group A1 (P 0.001) at all time points. The hsCRP and IL-6 levels in groups A2 and B2 increased with time and reached the maximum level 1 week after the second intervention, and then gradually decreased. Atherosclerotic plaques, fibrous cap, and calcium salt deposits were apparent in the rats of group B1, whereas no obvious atherosclerotic changes were observed in the rats of groups A2 and B2. Conclusion: Periodontal interventions resulted in acute, short-term systemic inflammation. However, it was beneficial in long-term as it improved the carotid artery integrity. Keywords: atherosclerosis, high-sensitivity C-reactive protein, interleukin 6, periodontal intervention, periodontitis