Macrophage depletion in old mice improves disease recovery. Periodontal disease was induced in old and young mice (n = 6/group) for a period of 7 d. At the end of the induction period, the ligatures were removed and the mice were allowed to recover for 7 additional days. Macrophages were depleted via treatment with PLX3397 throughout the recovery period. After the 7-d recovery period, the maxillae were isolated and analyzed. PLX3397 treatment resulted in a significant decrease in macrophage quantity within the periodontium at the end of the recovery period (A). Treatment with PLX3397 did not have an effect on tartrate-resistant acid phosphatase–positive (TRAP+) osteoclast cell surface/bone surface or TRAP+ osteoclast number per bone surface in the periodontium of old or young mice (B, C). Treatment resulted in significantly decreased proinflammatory cytokine expression within the gingiva of old mice as measured by quantitative real-time polymerase chain reaction (D). In addition, treatment with PLX3397 resulted in significantly greater bone volume fraction (BV/TV) and bone mineral density (BMD) as measured by micro–computed tomography (F) compared to untreated controls. No treatment effect was demonstrated in young mice using the same analysis (E, G). Data presented as mean ± SD and mean ± SEM for D and E. *P < 0.05. **P < 0.01.