Abstract In this study, associations between periodontitis expression, serum levels of inflammatory markers and genetic factors were investigated. The periodontal status of 56 subjects with chronic periodontitis, 28 control subjects and 80 subjects with type I diabetes mellitus (DM) was examined. In addition, a reference group (n=178) with genetic but not with periodontal health data was included. The single nucleotide polymorphisms of CD14 -260, IL-6 -174, TNF-α -308, IL-10 -1082, IL-1A -889, IL-1B +3954, and TLR4 +896 were determined using PCR with RFLP or allele-specific primers, and comparisons of the genotype frequencies were made between the study groups and reference subjects. The serum concentrations of IL-6 and sCD14 were assayed using ELISA. The distributions of all the studied genotypes were similar in the periodontitis and the reference subjects. However, in the periodontitis group, the carriage of the T-containing genotype of the CD14 -260 and the GG genotype of the IL-6 -174 associated significantly with the extent of periodontitis, indicating that genetic factors play a role in the pathogenesis of the disease. Both the extent of periodontal infection and the IL-6 -174 genotype were significant determinants for the serum IL-6 level, subjects carrying the GG genotype having significantly higher serum IL-6 levels than those carrying the CC/CG genotype. The serum level of sCD14 was significantly higher in subjects carrying the T-containing than the CC genotype of the CD14 -260 in the control group but not in the periodontitis group, suggesting that severe periodontal infection overshadows the influence of the genotype on serum sCD14 level. Overall, the serum studies indicated that periodontal infection is associated with a low-grade systemic inflammatory response. Type 1 DM subjects carrying the GG genotype of the IL-6 -174 had a higher extent of periodontitis when compared with those carrying the CG/CC genotype. Our results also suggest that the IL-6 -174 genotype is a more significant determinant of the extent of periodontitis in type 1 DM than glycemic control.