An osteotomy of the distal femoral diaphysis was fixed with an intramedullary self-reinforced poly-L-lactide (SR-PLLA) rod in 22 and with a metallic rod in 38 skeletally mature rabbits. Histomorphometric and quantitative computed tomography (QCT) were performed to assess time-related changes in the consolidation process of the osteotomy of cortical bone and development of the external callus. The follow-up times were 8, 16, 24, and 48 weeks for radiologic and 16, 24, and 48 weeks for histologic studies; 19/22 of the SR-PLLA and 34/38 of the metallic fixed osteotomies healed during the observation periods. On microscopic evaluation, no difference was found in histologic parameters such as external callus area and fraction, and endosteal callus area and fraction between SR-PLLA and metallic fixed osteotomies. The total external callus area increased up to 16 weeks and subsequently decreased linearly over time in both experimental groups. However, the mean endosteal bone area and fraction decreased after 16 weeks in metallic fixated femora, while in the SR-PLLA fixated femora, both these values increased, being greater in the SR-PLLA group. The mean external callus QCT density decreased after 8 weeks in both experimental groups, the decrease being greater in the SR-PLLA group. Nevertheless, no significant difference was detected between SR-PLLA and metallic fixed femora in any of the follow-ups. These results suggest that both SR-PLLA and metallic rods are suitable in the fixation of femoral shaft osteotomies in rabbits. Furthermore, SR-PLLA rod fixation seems to have a minor stress-shielding effect.