Summary Objective The purpose of this study was to compare the effectiveness of minocycline on treating experimentally induced periodontitis in rats when administered either as a systemic subantimicrobial dose or as a topical ointment. Design Thirty-two adult male Sprague–Dawley rats in four experimental groups—(1) model group; (2) systemic subantimicrobial dose of minocycline (5 mg/kg/day) treatment group; (3) topical subgingival dose of minocycline (2 mg/animal/week) treatment group; (4) control group. Experimentally induced periodontitis—silk ligatures were placed around the crevices of the second molar teeth and the animals fed a 10% sucrose drink. Assessment was carried out at days 28 and 56 using a number of different visual, histological and ultrastructure approaches. (1) Visual assessment—tooth mobility, gingival index and alveolar bone loss. (2) Histological examination—monocyte infiltration and resorption lacunae with osteoclasts. (3) Transmission electron microscopy (TEM)—morphological transformation of fibroblasts and osteoclasts. The collected data were analysed for statistical significance using the analysis of variance statistical test. Results Minocycline significantly reduced tooth mobility, gingival index and alveolar bone loss when administered either systemically or as a topical ointment compared to the model group ( P < 0.01). However, the alveolar bone loss was significantly less ( P < 0.01 in the systemic treatment group compared to the local treatment group. Monocyte infiltration and resorption lacunae with osteoclasts were significantly less in the both treatment groups compared to the model group ( P < 0.01). The osteoclasts failed to form a ruffled border in the systemic treatment group. Conclusion Topical treatment significantly reduces gingivitis while systemic treatment is beneficial in terms of inhibiting alveolar bone loss.