Macrophage colony-stimulating factor 1 (CSF1) controls the proliferation, differentia-tion and function of osteoclasts and macrophages. Exogenous CSF1 has been shown to have anabolic effects on multiple tissues, including the ability to promote bone repair. Clinical and pre-clinical CSF1 applications have been constrained by its short circulating half-life. This limitation was overcome by engineering a chimeric CSF1 molecule, CSF1-Fc, to by-pass renal clearance, facilitating a more potent and long-acting CSF1-receptor signaling. We tested weekly and biweekly CSF1-Fc treatment regimens over a 4-week period in adult 12-16-week-old female and male mice. Histomorphometric analysis showed F4/80+ osteal macrophage number was unchanged after either regimen, while TRAP+ osteoclast surface/trabecular bone surface was significantly increased only after biweekly CSF1-Fc treatment (p=0.0071) irrespective of gender. Hence, weekly CSF1-Fc treatment had minimal impact on bone-related myeloid cell populations under homeostatic conditions. To assess whether this non-myeloproliferative CSF1-Fc regimen primed regenerative mechanisms, we inves-tigated the therapeutic potential in bone regeneration using the MouseFix internally plated femoral fracture model. Weekly CSF1-Fc treatment for 4 weeks post-fracture significantly increased bone marrow macrophages as examined by flow cytometry (p<0.0001) but did not alter osteoclast surface/trabecular bone surface on the contralateral/unfractured limb. Torsional strength testing of the fractured femora revealed CSF1-Fc treatment significantly increased fracture maximum torque (+44%). Collectively, our results indicate that targeting macrophages using a weekly CSF1-Fc treatment regimen is a promising fracture therapeutic to promote bone regeneration.