Aim or purpose: To investigate the impact of different rosiglitazone doses on macrophage polarization states in periodontal tissues and the alveolar bone destruction during periodontitis progression in rats. Materials and methods: Forty 6-week-old male SD rats were randomly divided into four groups: control group (C), periodontitis group (P), low-dose rosiglitazone group (L), and high-dose rosiglitazone group (H). Experimental periodontitis was established through orthodontic wire ligation around the first molars. Three groups received daily oral gavage for 3 weeks with either: (P) sterile saline (0.9% Nacl,1mg/Kg), (L) 5 mg/kg rosiglitazone and (H) 10 mg/kg rosiglitazone. Mandibles were harvested for Micro-CT scanning. The periodontal tissues were assessed for macrophages immunofluorescence staining, IL-1β and IL-10 immunohistochemical staining and TRAP staining for osteoclasts. All procedures was approved by the Animal Ethics Committee. Data were analyzed by one-way ANOVA using SPSS26. Results: MicroCT (BV/TV): C > L > H > P; M1 macrophages: P > L > H > C; M2 macrophages: L > H > P > C; M1/M2 ratio: P > C > L and H; IL-1β expression: P > H, L and C; IL-10 expression: L > H and P > C; TRAP+ osteoclasts: P > H > L > C; ‘and’ means no statistically significant differences, other data p<0.05. Conclusions: Rosiglitazone promoted M2 macrophage polarization and increased IL-10 expression while reducing M1 macrophage infiltration as well as M1/M2 ratio, and IL-1β levels in periodontal tissues. Notably, the low-dose group showed better outcomes in mitigating periodontal bone loss compared to the high-dose treatment.