Periodontitis is an inflammatory process that ultimately results in tooth loss. Although the primary etiologic agent for periodontitis is bacteria, the majority of periodontal tissue destruction is thought to be caused by an inappropriate host response. Reactive oxygen species (ROS) have been known to be involved in periodontal tissue destruction. We treated human gingival fibroblasts with lipopolysaccharide (LPS) obtained from E. coli and the periodontopathogens Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, and examined their inflammatory responses in the presence and absence of the antioxidant N-acetylcysteine (NAC). LPS enhanced ROS production, as well as, expression of pro-inflammatory cytokines such as interleukin-$1{eta}$, interleukin-6, interleukin-8 and tumor necrosis factor-${alpha}$, and the production and activation of MMP2. NAG suppressed all LPS-induced inflammatory responses examined, suggesting that LPS-induced ROS may playa major regulatory role in these responses in gingival fibroblasts. In addition, NAG prevented LPS-induced activation of p38 MAPK and JNK but not phosphorylation and subsequent degradation of 1kB. These results indicate that NAG exerts anti-inflammatory effects in LPS-stimulated gingival fibroblasts, functioning at least in part via down-regulation of JNK and p38 MAPK activation. Furthermore, this work suggests that antioxidants may be useful in adjunctive therapies that complement conventional periodontal treatments.