Excessive intake of a high-fat diet (HFD) results in overweight, obesity and the development of insulin resistance, adipose tissue macrophage infiltration and significant increases in inflammatory biomarkers. Bone marrow mesenchymal stem cells (MSCs) are directly involved in hematopoiesis and angiogenesis, and are currently receiving considerable attention due to their remarkable applications to cell therapy. In obese people, hematopoiesis and angiogenesis can be affected as a result of the unbalanced production of several kinds of mediators, such as VEGF. VEGF production is regulated by transcription factors such as Stat-3, which can also activate other transcription factor regulators such as c-Myc, which is closely correlated to cell proliferation. Two-month-old male Wistar rats were fed an HFD and bone marrow MSCs were isolated. The cell cycle, Stat-3 and c-Myc expression, and VEGF production were evaluated. HFD animals showed greater adipose tissue mass as well as higher blood cholesterol, leptin, and C-reactive protein levels. MSCs from the HFD group showed a higher percentage of cells in the S/G2/M phase, increased production of VEGF and higher expression of c-Myc and Stat-3. These data led us to infer that HFD induces alterations in bone marrow MSCs, which could modify their modulatory capability and affect their use in cell therapies.