Abstract: Objective To investigate the effect of topical application of minocycline hydrochloride ointment assisted with subgingival scaling and root planing on periodontium of patients with chronic periodontitis. Methods Total 152 patients with chronic periodontitis in the First Affiliated Hospital of Wenzhou Medical University were selected and divided into two groups according to the random number method, each group 76 cases. All patients were given subgingival scaling and root surface roughness. The control group was given iodine glycerol, and the observation group was given intravenous minocycline ointment. After the treatment, the periodontium related indexes[periodontal pocket depth (PD), attachment level (AL), plaque index (PLI), gingival bleeding index (SBI)], the inflammatory factor[interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor (TNF)-α], clinical efficacy and adverse reactions of the two groups were compared. Results The total effective rate of the observation group was 94.74%, which was significantly higher than that of the control group (75.00%), P<0.05. After the treatment, PD, AL, PLI, SBI of the two groups were significantly decreased (P<0.05), and the observation group was significantly lower than the control group (P<0.05). After the treatment, there were no significantly difference on IL-6 levels in both two groups (P>0.05). The CRP and TNF-α of the observation group were significantly reduced (P<0.05), and significantly lower than that of the control group (P<0.05). The adverse reaction rate of the observation group and control group were 6.58% and 5.26%, respectively, which were not statistically significant (P>0.05). Conclusion Local application of minocycline hydrochloride ointment assisted with subgingival scaling and root canal surgery has a significant effect on chronic periodontitis. It can improve periodontal symptoms, the mechanism might be related to the regulation of the levels of CRP and TNF-α.