The purpose of this study is to investigate the potential of the systemic administration of different doses of rosuvastatin (RSV) on autogenous grafted critical-sized cortical bone defects. Twenty-four rats were divided into three groups: Group C (control), Group RSV-2 and Group RSV-5. A 5-mm diameter critical size defect was created in the calvarium of each animal. In Group C, the defect was filled by autogenous graft only and rats were given saline solution with oral gavage for 28 days. In Group RSV-2 defects were filled with autogenous graft and rats were given 2 mg/kg rosuvastatin with oral gavage for 28 days. In Group RSV-5 defects were filled with autogenous graft and rats were given 5 mg/kg rosuvastatin with oral gavage for 28 days. All animals were euthanized at 28 days postoperative. Stereologic and micro-CT analyses were performed. New bone area (NBA) and connective tissue volumes were measured. Stereologic analysis showed that Group RSV-5 and RSV-2 had significantly more new bone at 4 weeks compared with group C. Connective tissue volumes were also significantly higher in RSV applicated groups. New bone and connective tissue volumes' difference were not statistically significant between RSV groups. Micro-CT results were similar with stereologic analyses. Orally administered RSV enhances bone regeneration in critical size calvarial rat defects filled with autogenous graft furthermore possible inflammatory effect should be investigated. (C) 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.