Abstract. The aim of the present study was to investigate the local effect of 10% doxycycline and 1% alendronate combined with poly(lactic-co-glycolic acid) (PLGA) on bone repair. Thirty rats were divided into three groups, as follows: control group (CG), drug group (DG), and vehicle-PLGA group (VG). Bone defect was created in the right femur and filled with the following: blood clot (CG); PLGA gel, 10% doxycycline and 1% alendronate (DG); or vehicle-PLGA (VG). The animals were euthanized 7 or 15 days after surgery. Bone density, bone matrix and number of osteoclasts were quantified. At 7 days, the findings showed increased density in DG (177.75±76.5) compared with CG (80.37±27.4), but no difference compared with VG (147.1±41.5); no statistical difference in bone neoformation CG (25.6±4.8), VG (27.8±4), and DG (18.9±7.8); and decrease osteoclasts in DG (4.6±1.9) compared with CG (26.7±7.4) and VG (17.3±2.7). At 15 days, DG (405.1±63.1) presented higher density than CG (213.2±60.9) and VG (283.4±85.8); there was a significant increase in percentage of bone neoformation in DG (31.5±4.2) compared with CG (23 ±4), but no difference compared with VG (25.1±2.9). There was a decreased number of osteoclasts in DG (20.7±4.7) and VG (29.5±5.4) compared with CG (40±9.4). The results suggest that the association of 10% doxycycline and 1% alendronate with PLGA-accelerated bone repair.