Abstract： Objective To investigate the mechanism underlying the influence of interleukin-6(IL-6)on tumor necrosis factor-alpha(TNF-α)expression in the gingival tissue of rats with peri-implantitis.Methods Forty rats were randomly assigned into sham operation group(sham group),peri-implantitis group(PI group),PI+IL-6 inhibitor Tocilizumab group(Tocilizumab group),and PI+Tocilizumab+nuclear factor-kappa B(NF-KB)/p65 activator lipopolysaccharide(LPS)group(LPS group),with 10 rats in each group.The periodontal pocket depth(PPD)in peri-implant soft tissue,bleeding on probing(BOP),bleeding index(BI)and gingival index(GI)were detected.Peri-implant bone height and bone density were measured by Micro-CT.Inflammatory infiltration in peri-implant gingival tissue was observed by hematoxylin and eosin(H&E)staining.The mRNA levels of IL-6 and TNF-α in peri-implant gingival tissue were examined by real-time reverse transcription polymerase chain reaction(RT-PCR).Protein level of p-p65 in gingival tissue was examined by Western blot.Results Compared with those of the sham group,PPD(proximal cheek,distal cheek,proximal tongue,distal tongue),BOP,BI and GI were significantly higher in the peri-implant soft tissues of rats in the PI group(P＜0.05).Compared with those of the PI group,PPD(proximal cheek,distal cheek,proximal tongue,distal tongue),BOP,BI and GI were significantly lower in the peri-implant soft tissues of rats in the Tocilizumab group(P＜0.05).The PPD(proximal buccal,distal buccal,proximal tongue,distal tongue),BOP,BI and GI were significantly higher in the peri-implant soft tissues of LPS group compared with those of the Tocilizumab group(P＜0.05).Compared with the sham group,the peri-implant bone height and alveolar bone density were significantly lower,and the mRNA levels of IL-6 and TNF-α and protein level of p-p65 were significantly higher in the PI group(P＜0.05).Compared with those of the PI group,the peri-implant bone height and alveolar bone density were significantly higher,and the mRNA levels of IL-6 and TNF-α and protein level of p-p65 were significantly lower in the Tocilizumab group(P＜0.05).Compared with the Tocilizumab group,the peri-implant bone height and alveolar bone density were significantly lower,and the mRNA levels of IL-6 and TNF-α and protein level of p-p65 were significantly higher in the LPS group(P＜0.05).Conclusion IL-6 inhibitor attenuates the development of peri-implantitis in rats by inhibiting the release of the pro-inflammatory factor TNF-α via inhibiting the NF-κB pathway in dental pulp tissue.