Nuclear factor-kappaB (NF-kappaB) is a transcription factor which plays a pivotal role in the induction of genes involved in physiological processes as well as in the response to injury and inflammation. Dithiocarbamates are antioxidants which are potent inhibitors of NF-kappaB. We postulated that pyrrolidine dithiocarbamate (PDTC) would attenuate inflammation. In the present study, we have investigated the effects of PDTC, in a rat model of periodontitis. Periodontitis was induced in rats by placing around the lower left first molar a 2/0 braided silk. At day eight the gingivomucosal tissue encircling the mandibular first molar was removed for biochemical and histological analysis. At day eight ligations significantly induced an increase neutrophil infiltration as well as the gingivomucosal tissue expression of TNF-alpha and iNOS as well as nitrotyrosine formation and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitonial injection of PDTC (10 mg/kg daily for eight days) significantly reduced all of the parameters of inflammation as described above. These data demonstrate that PDTC exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage associated with ligature-induced periodontitis.