Successful pregnancy requires uterine vessel remodelling during early pregnancy to allow placental, hence fetal, growth. Macrophages are crucial for immune tolerance and embryo implantation yet their role in promoting maternal vascular adaptations remains unclear. We hypothesised that macrophages modulate vascular remodelling in early pregnancy to permit early placental development. We utilised the CD11b-Dtr mouse model to transiently deplete macrophages on day 5.5 post coitum (pc) using diphtheria toxin (DT) which binds the transgenic monkey diphtheria toxin receptor (Dtr) in CD11B+ macrophages. In wild-type control females, DT administration elicits no adverse effects on macrophages or pregnancy. DT administration to pregnant CD11b-Dtr females caused >90% macrophage depletion and substantial fetal loss, partly attributable to decreased serum progesterone and ovarian haemorrhage. Then, in separate cohorts, we either administered progesterone pellets or transferred wild-type bone marrow-derived macrophages (BMDM) to macrophage-depleted mice. Both progesterone and BMDM increased pregnancy rate on day 7.5 pc (81% and 78% vs 43%, p<0.01). At this time maternal vascular remodelling was impaired in macrophage-depleted mice (p<0.05). Progesterone treatment was insufficient to rescue uterine vessels remodelling as assessed by lumen diameter but BMDM restored it to control levels. RNA expression profiling of over 600 genes in the uterus revealed that of the >250 genes dysregulated, BMDM transfer restored normal gene expression of >15% more dysregulated genes than did progesterone treatment, while markers of embryo invasion and endothelial cell function remained aberrant in progesterone-treated mice. Importantly, BMDM rescued genes are involved in the regulation of vasculature development pathway (FDR=2.23e-08). This study demonstrates that macrophages are essential for the maternal vascular adaptations required during early pregnancy. Defining how macrophages drive vascular remodelling and their interaction with other immune cells may contribute to understanding the causes of, and developing effective therapeutics for women with pregnancy complications associated with vascular maladaptations.