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Aim: The aim of this experimental animal model study is to investigate the effects of caffeic acid phenethyl ester (CAPE) and melatonin on the maturation of newly-formed regenerated bone in distraction osteogenesis., Methods: Unilateral femoral lengthening(extension) was applied to 39 adult male Wistar albino rats, which were randomly allocated to 3 groups of 13; control, melatonin and CAPE groups. Through a 7-day latent waiting period and 15 days of distraction, melatonin of 25 mg/kg and CAPE of 10 μmol/kg were administered to the respective groups. The animals were sacrificed on Day 82. Radiographic, histological and biomechanical evaluations were made and measurements were taken., Results: At the end of 82 days, the distraction osteogenesis area was seen to be completely filled with new bone formation in all 3 groups both radiologically and histologically. Biomechanically, the maximum torsional fracture strength (Maximum Torque (N-m)) of the melatonin group was higher compared to that of the control group, although it was not statistically significant (p > 0.05). The maximum torsional momentum of the CAPE group was statistically significantly high (p < 0.05). The degree of rigidity (N-m/deg) of both the melatonin and CAPE groups was higher than that of the control group and the CAPE group was found to be statistically significantly higher than the melatonin group (p < 0.05)., Conclusion: Melatonin and CAPE increase the maturation of new bone in distraction osteogenesis. These effects are probably due to the reducing effect on bone resorption by inhibiting NF-κB and free oxygen radicals.