The development of the mononuclear phagocyte system (MPS) is controlled by signals from the CSF1 receptor (CSF1R). Homozygous mutation of the Csf1r locus (Csf1rko) in inbred rats led to the loss of non-classical monocytes and tissue macrophage populations, reduced postnatal somatic growth, severe developmental delay impacting all major organ systems and early mortality. The developmental impacts overlap with growth hormone/insulin-like growth factor (GH/IGF1) deficiency and Csf1rko rats lacked circulating IGF1. The liver is the main source of circulating IGF1. Expression profiling of juvenile wild-type and Csf1rko livers identified 2760 differentially expressed genes associated with the loss of macrophages, severe hypoplasia, delayed hepatocyte maturation, disrupted lipid metabolism and dysregulation of the GH/IGF1 system. Transfer of WT bone marrow at weaning restored circulating IGF1 and reversed the mutant phenotypes enabling long term survival and fertility. Phenotypic rescue was achieved without reconstituting blood monocytes or CSF1-responsive bone marrow progenitors. The results demonstrate that CSF1R-dependent macrophages control the growth and maturation of the liver and regulate the GH/IGF1 axis.