Background Porphyromonas gingivalis is a gram-negative bacterium that is an important etiologic agent of human adult periodontitis. The goal of the study was to test the hypothesis that two different isoforms, PgLPS1435/1449 and PgLPS1690 exhibit differences in their capacity to stimulate systemic versus local responses compared to E. coli LPS. Methods Lipopolysaccharide (LPS) was inoculated into the scalp of mice and the response was measured locally at the site of site of inoculation and systemically in the heart/aorta. VCAM-1 was assessed at the protein level by ELISA and VCAM-1, E-selectin, and ICAM-1 at the RNA level of RNase protection assay. Serum TNF-α levels were also measured. Results E. coli LPS and both isoforms of P. gingivalis LPS groups were relatively potent in stimulating expression of inflammatory markers with E. coli LPS being somewhat more potent. In contrast, when the systemic response was measured in the heart/aorta, E. coli but not P. gingivalis LPS significantly induced inflammatory markers. At moderate to low doses (1 and 10 ug per injection) serum TNF–α levels were minimally induced by P. gingivalis LPS compared to E. coli LPS. Conclusion The results indicate that both forms of P. gingivalis LPS stimulate an inflammatory response when injected into connective tissue but are minimally stimulatory when a systemic response is measured. In contrast E. coli LPS is a potent stimulus at both the systemic and local level.