Purpose: The aim of the present study is to evaluate the influence and efficacy of autologous platelets on bone regeneration in a rabbit defects model. Materials and Methods: A total of 12 critical size tibial defects were produced in six New Zealand rabbits: A total of six defects were filled with autologous platelet gel (APG) and six defects were maintained as untreated controls. No membranes were used to cover the bone osteotomies. The histology and histomorphometry were performed at four weeks on retrieved samples of both groups. Results: No complications were reported in any of the animals nor for the defects produced. A significantly higher lamellar and woven bone percentage was reported for the APG group with a lower level of marrow spaces (p < 0.05). Evidence of newly formed bone was found in the superficial portion of the bone defect of APG samples where no aspects of bone resorption were observed. Conclusions: The evidence of the present research revealed that APG increases new bone formation restricted to the cortical portion and induces more rapid healing in rabbit bone defects than in untreated defects.