Mesenchymal stromal/stem cells (MSC) are an important multipotent cell population within in the bone-marrow microenvironment. MSC contribute to this microenvironment either in their stem cell state or as differentiated progeny (i.e. osteoblasts or adipocytes).  MSC and their progeny are known to play a critical role in maintaining the bone-marrow hematopoietic stem cell (HSC) niche, both through direct and indirect signalling.  Recent work has demonstrated a species-specific preference for human MSC when human HSC are transplanted intra-venously into irradiation conditioned immune compromised mice.  These studies were completed with a combination of human HSC and MSC, and did not quantify if irradiation enhanced human MSC engraftment when these cells were transplanted without human HSC.  Herein, we quantified the engraftment of human MSC in the bone marrow of NOD-SCID IL2γ^-/- (NSG) mice either conditioned or not conditioned with 2Gy irradiation.  Human MSC (5x10⁵) were injected intra-femorally into the right femur while the left femur (control) received a saline injection.  Transplanted mice were imaged weekly using an In Vivo Imaging System (IVIS) to quantify the bioluminescence emanating from the luciferase labelled human MSC.  At 8 weeks, the animals were euthanized, and harvested femurs were fixed overnight in 4% paraformaldehyde, decalcified in EDTA and paraffin embedded prior to sectioning to enable histological and immunohistochemical analyses.  Irradiation was found to increases the level of MSC engraftment significantly by week 2.  IVIS results also suggested that human MSC engraftment persisted significantly longer in irradiated mice.  By further understanding how the human MSC engraft long-term in mice, we hope to further optimise the use of MSC within mouse models. This is critical, especially in the development of in vivo model systems that require extended timelines in order to study the impact of human MSC on processes such as human HSC engraftment or human cancer bone metastasis.