Periodontal disease is a chronic inflammation of the gingiva resulting in the destruction of periodontal tissue. Porphyromonas gingivalis (Pg), a gram-negative bacterium, appears to play a role in the development of periodontal disease. Lipopolysaccharide (LPS), a component of the gram-negative bacterial cell wall, plays a role in periodontal tissue destruction. We have shown that intragingival application of Pg-derived LPS (Pg-LPS) in rats increases gingival TNF-α without affecting IL-6 (Taguchi et al., Int. J. Oral Sci., 2015). Since periodontal infection is known to be a potential threat to general health, we examined the influence of intragingival application of Pg-LPS on plasma TNF-α and IL-6 levels in urethane-anaesthetized rats. For comparison, effects of LPS derived from Escherichia coli (Ec-LPS) were also studied. Male SD rats were used. The external jugular vein was cannulated and connected via Teflon tubing to a blood sampling system. Either Pg-LPS (1 µg), Ec-LPS (6 µg) or vehicle was injected into gingiva of upper incisors via a microsyringe, with 500 µl of blood sampled every 1 hr. Plasma TNF-α and IL-6 levels were determined by enzyme-linked assays. Unlike IL-6, basal plasma TNF-α was lower than the detection limit (5 pg/ml). Pg-LPS failed to affect IL-6 levels but increased TNF-α. Neither IL-6 nor TNF-α were altered by Ec-LPS. These results suggest that increased Pg-LPS in gingiva may have systemic effects through induction of plasma TNF-α.