The purpose of this study is to investigate the potential of the local administration of different doses of rosuvastatin (RSV) on autogenous grafted critical-sized cortical bone defects. Twenty-four rats were divided into 3 groups: Group C (control), Group RSV-0.1, and Group RSV-1. 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 and sterile saline-treated absorbable collagen sponge (ACS) was applied. Defects in the experimental groups (groups RSV-0.1 and RSV-1) were grafted by autogenous graft and ACS with saline solution containing 0.1- and 1-mg RSV were applied. All animals were euthanized at 28 days after operation. Stereologic and micro-computed tomography (CT) analyses were performed. New bone area and connective tissue volumes were measured. Stereologic analysis showed that the difference between group RSV-1 with a mean bone formation of 1.79 +/- 0.06mm(3) and groups RSV-0.1 and control (C) was statistically significant (P0.05) with a mean bone formation of 1.29 +/- 0.28mm(3) and 1.08 +/- 0.12mm(3), respectively. Connective tissue volume was also significantly higher in 1-mg RSV applicated group. Micro-CT results were similar with stereologic analyses. Local administered 1-mg RSV enhances bone regeneration in critical-size calvarial rat defects filled with autogenous graft.