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Objective: To evaluate the effect of mono and combined therapy of low dose doxycycline (LDD) and Bisphosphonate (BPs) on ligature-induced periodontitis in Diabetic rats by immunohistochemical analysis of the expression of osteoprotegerin (OPG) and by immunohistomorphometric analysis. Methods: Fifty adult Wistar rats were divided into five study groups as follows: 1) group 1 = diabetes control; 2) group 2 = diabetes + periodontitis; 3) group 3 = diabetes + periodontitis + LDD; 4) group 4 = diabetes + periodontitis + clodronate; and 5) group 5 = diabetes + periodontitis + LDD + clodronate.LDD and clodronate were given as a single agent or as combination therapy during the 7 days of the post-experimental periodontitis period.On day 7, the rats were sacrificed, the mobility of the toothwas recorded, and block biopsies were removed. The gingival tissues were analyzed histologically and immunohistochemically for expression of OPG. Data analysis was performed statistically by Kruskal-Wallis and post hoc Tukey tests. Results: The greatest mean value was recorded in group5, followed by group 4, then group 3. Using Tukey's post hoc test; there was a significant difference (p<.0001) between groups1, 2, 4 and 5 respectively while non significant difference was found between group 1and 3. Comparing group 2 with groups 3, 4 and 5 a significant difference was found. Comparing groups 3 with groups 4and 5 non significant difference was found between groups 3 and 4 while a significant difference was found between groups 3 and 5. Lastely, non significant difference was found between groups 4 and 5. Codex : 07/1601 dentaljournal.forgirls@yahoo.com KEYWORDS Bisphosphonate; diabetes mellitus; doxycycline; periodontium.