The role of colony stimulating factor-1 (CSF-1) in the regulation of osteoclasts and bone remodeling suggests that CSF-1 may also be involved in regulation of bone healing. The ability of CSF-1 to promote healing of bone defects was tested in a rabbit model. Twenty-four New Zeeland rabbits were included in the study. Animals were assigned to two groups: the control group (n = 12) was treated by plate fixation. The animals in the second group (n = 12) were also stabilized by conventional plating and received additionally CSF-1 for 2 weeks systemically. Histologic, histomorphometric, and radiologic examinations were performed to evaluate the healing process at 4, 8, and 12 weeks following surgery. Animals that were treated by CSF-1 produced a significantly higher amount of mineralized bone over the first 8 weeks after fracture compared to the control animals. Furthermore, a higher number of osteoclasts was found in CSF-1-treated animals within the first 8 weeks, compared to the controls. The present data emphasize for the first time the importance of CSF-1 in the bone healing. The use of CSF-1 in addition to conventional fixation might be a novel approach for the treatment of bone defects.