Bone marrow (BM) vascular regeneration is absolutely necessary for hematopoietic recovery after myeloablation, yet the mechanisms of vascular regeneration are poorly understood. We found that, two weeks after lethal irradiation and BM transplantation, mice transplanted with 20x106 bone marrow nucleated cells (BMNC) had ∼6-fold more CD45-Ter119-CD31+CD105+ endothelial cells (6.9x103 vs 0.96x103 p < 0.001), increased blood vessels (195 vs 97 vessels per segment, p < 0.05), and reduced BM vascular leakage (4.8 vs 9.3 ng/mL of extravasated Evans Blue dye p < 0.001) than mice transplanted with 105 BMNC. These indicated that hematopoietic cells crosstalk with the vasculature to promote vascular regeneration. Adoptive transfer of the major BM hematopoietic populations into lethally irradiated mice demonstrated that only Gr1+CD115- granulocytes are capable of promoting vascular regeneration (2.52x103 for granulocyte treated mice vs 0.9x103 for PBS p < 0.01, 0.3x103 for B- and T-cells, 0.7x103 for monocyte/macrophages, and 0.3x103 for erythroid lineage treated mice). Granulocyte transfer also promoted survival (granulocytes=100%, PBS=50% p < 0.05), probably due to faster recovery of blood platelets and red blood cells in peripheral blood (granulocytes= 4.5x107 PLT/ml and 6.2x109 RBC/ml; PBS= 2.1x107 PLT/ml and 4x109 RBC/ml, p < 0.01). To investigate the mechanisms of granulocyte-mediated vascular recovery, we profiled expression of angiogenic factors. We found that granulocytes were the main source of TNFα in the BM and Tnfrsf1a (the TNFα receptor) was specifically upregulated in BM endothelial cells. To test whether TNFα is necessary for vascular regeneration, we myeloablated WT or Tnfα-/- mice with 5-fluorouracil. Tnfα-/- mice showed dramatically reduced survival (13% vs 93% p < 0.001) and reduced numbers of BM endothelial cells (4.2x103 vs 9x103 p < 0.05) when compared with WT mice. Taken together these results indicate that TNFα is necessary for survival and vascular regeneration after myeloablation. In adoptive transfer experiments only WT, but not Tnfα-/- granulocytes promoted vascular regeneration (PBS= 0.9x103, WT= 5.24x103, and Tnfα-/- = 3.0x103endothelial cells/femur, p < 0.05). These results demonstrate that BM granulocytes crosstalk with the endothelial cells via TNFα to promote vascular and hematopoietic regeneration.