Objective. We evaluated the efficacies of antimicrobial photodynamic therapy (aPDT) and minocycline ointment (MO) on clinical and bacteriological markers and the local host inflammatory response. Materials and Methods. A total of 30 patients with chronic periodontitis were randomly assigned to two groups. Selected periodontal pockets (probing depth 5-7 mm with bleeding on probing) were treated with aPDT or MO. Measurements of clinical parameters and the collection of gingival crevicular fluid (GCF) and subgingival plaque were performed at baseline, and at 1 and 4 weeks after treatment. Quantification of periodontopathic bacteria in the sulcus and a multiplex bead immunoassay of ten inflammatory cytokines in the GCF were performed. Results. Local MO administration exhibited a significant decrease in scores for clinical parameters (P&lt
0.01) and a significant reduction in bacterial counts (P&lt
0.01) and interleukin-1β and interferon-γ levels at 1 and 4 weeks after treatment (P&lt
0.01). No significant changes were observed in the aPDT group, except in clinical parameters. Conclusions. Although our study had some limitations, we found that while local administration of MO may slightly help to improve clinical, microbiological, and crevicular cytokine levels in periodontal pockets, aPDT did not show any effects. This trial is registered with the UMIN Clinical Trials Registry UMIN000013376.