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 (μCT) 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 ± 0.06 mm3 and groups RSV-0.1 and control (C) was statistically significant (P ≤ 0.05) with a mean bone formation of 1.29 ± 0.28 mm3 and 1.08 ± 0.12 mm3, 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.