Background: Angiogenesis is crucial for formation of a stable regenerate during distraction osteogenesis (DO). This experimental study evaluates if bone morphogenic protein-2 (BMP-2) and desferrioxamine (DFO), two agents which are known to induce neoangiogenesis in vivo , would increase angiogenesis and osteogenesis, and improve mechanical properties of bone regenerate in DO model. Methods: Twenty-four tibias of 24 New Zealand rabbits were osteotomized and fixed with semi-circular fixators. Three groups of 8 animals were formed. BMP-2 soaked scaffolds were used in the first group, whereas daily local DFO injections were made in the second group. Subjects in the control group did not receive any agents during the surgery or in the distraction period. The rabbits in all three groups underwent distraction at a rate of 0.6 mm/day for 15 days following the 7-day latent period. Animals were sacrificed on day 38, and the tibia were harvested for histological and mechanical examination of the regenerate. Results: All 24 rabbits survived the surgical procedure, and there were no side effects against the BMP-2 and local DFO. Three-point bending tests revealed a higher force (361 +/- 267 N.) required for fracture in Group 1 ( p : 0.018). Similarly, the bending moment in Group 1 (5.4 +/- 4.0 Nmm) was significantly higher than the other groups ( p : 0.021). There was no significant difference between the groups in terms of deflection and stiffness ( p > 0.05). Histologically, there was no statistical difference between the groups in terms of endochondral, periosteal, and intramembranous ossification and VEGF activity ( p > 0.05). Conclusion: BMP-2 and DFO stimulate angiogenesis by increasing VEGF activity. Angiogenesis is one of the most important mechanisms for the initiation and maintenance of new bone formation. Stimulation of angiogenesis in unfavorable biomechanical conditions may not be sufficient for ideal bone formation. (c) 2022 Elsevier Ltd. All rights reserved.