Objectives This study tested whether or not gene expression in human marrow stromal fibroblast (MSF) cells depends on light wavelength and energy density. Material and Methods Primary cultures of isolated human bone marrow stem cells (hBMSC) were exposed to visible red (VR, 633 nm) and infrared (IR, 830) radiation wavelengths from a light emitting diode (LED) over a range of energy densities (0.5, 1.0, 1.5, 2.0 Joules/cm2) Cultured cells were assayed for cell proliferation, osteogenic potential, adipogenesis, mRNA and protein content. mRNA was analyzed by microarray, and compared among different wavelengths and energy densities. Mesenchymal and epithelial cell responses were compared to determine whether responses were cell-type specific. Protein array analysis was used to further analyze key pathways identified by microarrays. Result Different wavelengths and energy densities produced unique sets of genes identified by microarray analysis. Pathway analysis pointed to TGF beta 1 in the visible red and Akt 1 in the infrared wavelengths as key pathways to study. TGF beta protein arrays suggested switching from canonical to non-canonical TGF beta pathways with increases to longer IR wavelengths. Microarrays suggest RANKL and TIMP 10 followed IR energy density dose response curves. Epithelial and mesenchymal cells respond differently to stimulation by light suggesting cell-type specific response is possible. Conclusions These studies demonstrate differential gene expression with different wavelengths, energy densities and cell types. These differences in gene expression have the potential to be exploited for therapeutic purposes and can help explain contradictory results in the literature when wavelengths, energy densities and cell types differ.