The purpose of this study was to determine the minimal inhibitory concentration (MIC) of cefuroxime axetil, semisynthetic cefalosporin, for some putative periodotopathogens; F. nucleatum, A. actinomycetemcomitans P. intermedia and P. gingivalis. To investigate the efficacy of cefuroxime axetil, several antibiotics, amoxicillin, metronidazole, and ciprofoxacine, were used as control. The MIC was measured by Murray's method. The MIC of cefuroxime axetil against some putative microbes, as a single use regimen, was relatively high in comparison with that of the other antibiotics used in this study. The MIC of cefuroxime axetil/metronidazole against some putative microbes, as a simultaneous regimen, was similar to that of the other antibiotics used in this study. The manimal level of cefuroxime concentration in gingival fluid was 9 µ/ml at 36hr after the first dose. In conclusion, within the limited experiment, metronidazole/ cefuroxime axetil therapy of periodontitis may provide a therapeutic benefits in reducing the periodontopathogens.