Stem cell therapy could have great potential for the treatment of a wide variety of diseases. Stem cells might have the ability to differentiate into a widespread cell types, and to repopulate and revitalize the damaged cells with healthy tissue, and improve its performance. We provide here the evidence supporting the critical use of stem cell as a treatment in disease conditions existing with high glucose complaint such as diabetes. The reduction of glucose stimulated cell proliferation and high glucose enhanced apoptosis in rat model, which may be a problem in therapeutic strategies based on ex vivo expansion of stem cell, and may also propagate the development of osteoporosis in high glucose complaint such as diabetes. This leads to the hypothesis that, high glucose could be more deleterious to stem cell therapy that may be due to the aggravation of oxidative stress triggered by high glucose. These findings may help to understand the possible reasons associated with high glucose induced detrimental effects on stem cells as well as provide novel therapeutic strategies for preventing the adverse effects of glucose on the development and progression of stem cells in patients with diabetes.