Abstract: [Abstract] Objective To explore the effect of metronidazole controlled release pellicles and minocycline hydrochloride sustained-release agent on the treatment of chronic periodontitis. Methods 82 cases with chronic periodontitis were randomly divided into A group (metronidazole controlled release pellicles) and B group (minocycline hydrochloride sustained-release agent).The following indices were analyzed between both groups: general parameters [probing depth (PD), attachment level(AL), plaque index (PLI) and sulcus bleeding index (SBI)] and inflammatory cytokines in gingival crevicular fluid [interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α)] before treatment, and 1week, 1 month and 3 months after treatment, as well as collagenase II activity (COL-Ⅱ) before treatment and 1 week, 1 month and 3 months after treatment. Adverse reaction was also analyzed between two groups. Results The number of cases cured in Group B was more than that in group A (P <0.05) 1 month after treatment, but the total effective rates was not different between two groups. Apart from PD 1 month after treatment, the general parameters, the inflammatory markers and COL-Ⅱ activity of gingival crevicular fluid of B group 1 and 3 months after treatment were better than those of A group ( P<0.01, except IL-6, IL-8 one month after treatment and PD, AL(P<0.05)). There was no significant difference in adverse reaction between two groups（P>0.05）. Conclusions The total effective rates of metronidazole controlled release pellicles and minocycline hydrochloride sustained-release agent on periodontitis were similar, but the long-term effect and inflammatory markers of gingival crevicular fluid and COL-Ⅱ activity of the latter was superior to the former.