OBJECTIVE To study the effects of chronic apical periodontitis (CAP) on the inflammatory response and initial lesion of aorta in hyperlipemic rats. METHODS Sprague-Dawley (SD) rats aged 14 weeks were randomly divided into 4 experimental groups (n = 8), namely, normal diet (ND), high-fat diet (HFD), CAP, and HFD + CAP. The rats were raised under controlled conditions and fed with diet specified for each group. All subjects were euthanatized after 14 weeks for histopathological analysis. Serum cytokines were analyzed to assess changes in gene and protein expression of aorta via enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Results were analyzed by one-way ANOVA. RESULTS Low-density lipoprotein cholesterol levels in rats in HFD + CAP group were significantly higher than those in other groups. By comparison, low-density lipoprotein cholesterol levels in rats in both the HFD and HFD + CAP groups were significantly lower than those in the other groups. No significant difference among all groups was observed in terms of CRP level. However, levels of IL-2, IL-6, and IL-10 increased in the experimental CAP rats compared with the control rats. mRNA expression levels of MCP-1, TLR-4, and NF-κB p65 were markedly elevated in rats in the HFD group compared with those in rats in the ND group. TLR-4 mRNA expression was significantly higher in rats in the HFD + CAP group than that in rats in the HFD group. CONCLUSIONS CAP mediated the high expression of cytokines and induced the initial inflammatory response in the aorta. Apical periodontitis may affect the level of inflammatory cytokines (IL-2, IL-6, and IL-10) depending on the immune response. CONCLUSIONS CAP may trigger a systemic inflammatory response and affect the aorta of patients.