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Objective: To investigate the clinical effect of metronidazole membrane combined with minocycline ointment on periodontal disease. Methods: 80 cases of patients with periodontal disease in our hospital from January 2014 to January 2016 were select and divided into observation group and control group. The patients in the observation group were treated with metronidazole membrane combined with minocycline ointment, and the patients in the control group were adopted metronidazole membrane. The curative effect, periodontal attachment index, plaque index, gingival index, tooth mobility degree and the levels of serum IL-2, IL-6, IL-8 and TNF were compared between the two groups. Results: After 4 weeks, The curative effect of the observation group (95.0%) was significantly higher than that of the control group (90.0% )(P<0.05); the periodontal attachment index, plaque index, gingival index and tooth mobility degree and the levels of serum IL-2, IL-6, IL-8 and TNF in two groups were all were significantly decreased (P<0.05), and the reduce degree of observation group was more obviously than that of the control group (P<0.05); no difference was found between the two groups as to pimples, nausea and gastrointestinal reaction and insomnia (P>0.05); the recurrence rate of the observation group (2.5%) was significantly lower than that of the control group (7.5%). Conclusions: Metronidazole membrane combined with minocycline ointment can enhance inhibition of periodontal pathogens, and improve the clinical effect, the periodontal condition and state of inflammation, and has less adverse reactions, low recurrence rate, worthy of application. [ABSTRACT FROM AUTHOR]