Objective: To investigate the effect of antibiotics application in perioperative period on carotid artery and serum interluekin-6 (IL-6) in chronic periodontitis (CP) rats with hyperlipidemia (HL) or diabetes mellitus (DM). Methods: The models of CP rats with HL or DM were established in different batches. The rats were divided into groups as follows: A and A' were normal control groups, n =7 in each group; B(HL) and B'(DM) were groups of HL and DM, n =7 in each; C(HL+CP) and C'(DM+CP) were groups of CP with HL and CP with DM, n =21 in each. After the establishment of the models, groups C and C' were divided into C1 and C1' non-intervention group, C2 and C2' simple tooth extraction group and C3 and C3' antibiotic-assisted tooth extraction, with 7 rats in each of the groups. Two time interventions were performed to extract experimental teeth (bilateral maxillary first and second molars) in groups C2, C2', C3 and C3'. Serum samples were collected at 5 time points before and after tooth extraction (T1: before the first tooth extraction; T2: one week after the first tooth extraction; T3, T4, T5: the first, third and fifth week after the second tooth extraction), respectively. The absolute content of IL-6 in serum was detected by enzyme-linked immunosorbent assay (ELISA). Ratio of the absolute content in the experimental groups and control groups were calculated as the relative content of IL-6. At the end of the experiments, all rats were euthanasia and the bifurcation vascular tissues of carotid artery were collected for the observation of the carotid artery pathology and plaque formation and the measurement of the thickness of carotid intimal-medial layer (IMT). Results: Carotid artery pathology observation showed the IMT in group C was significantly thickened and the group C2 was the most thickened one (compared with group A, P <0.01). Elastic fibers in groups C1 and C2 were disordered or even broken and disappeared, presenting typical atherosclerotic plaques, which were diffuse calcium salt deposits in the intimal-medial layers and protrude into the lumen. Elastic fibers in group C3 were ranged in ordered relatively without obvious fracture and the number of plaques was significantly reduced. The vascular walls in rats of groups B' and C' were incomplete, the IMTs had no obvious changes, elastic fibers were ranged disorderly and broken and the smooth muscle cells had vacuolar changes. In group C2', the vascular wall was significantly thinned and calcified plaques appeared in the artery, which showed multiple calcification lesions penetrating through the intimal-medial layer or even the whole layer. The vascular wall of group C3' was integrity and the elastic fibers arranged relatively clutter-free, the number of plaques was reduced. Results of detections of IL-6 showed the relative contents of IL-6 in groups B, B', C1, and C1' increased with time. At T3 time point, the relative contents of IL-6 in groups C2 and C3 reached the peak, C2 was 10.4 times of group A and C3 was 9.5 times of group A, and then decreased to different low levels. At T5 point, comparisons of the relative contents of IL-6 showed C3 < C2 < C1 (3.2 times, 5.4 times, 9.6 times of group A, respectively). The relative contents of IL-6 in groups C2' and C3' reached the peak at T2 point (4.9 times and 4.5 times of group A, respectively), and then decline with time. At T5 point, comparisons of the relative contents of IL-6 showed C3'< C2'< C1' (1.2 times, 1.4 times and 3.1 times of group A, respectively). Conclusions: Blood vessels were observed more obvious thickened in the tooth extraction without antibiotic of HL+CP rats with calcifications increase. Blood vessels of DM+CP rats became thin and fragile and even the integrity was damaged. Perioperative use of antibiotics might reduce the carotid artery lesions and decrease serum levels of inflammatory cytokines.