Background: Diabetes is one of the most important causes of mortality and morbidity all over the world. Renewal of functional pancreatic islets has been a goal of stem cell biologists since early 2000. Since that time, many studies have reported successful creation of glucose-responsive pancreatic beta-cells. Aim of work: This work aimed to study the effect of MSC.s alone and/or in combination with vitamin D3in Streptozotocin (STZ)- induced diabetic male albino rats to detect its potential therapeutic effect and its possible application to humans. Material and methods: Twenty-four male albino rats (150 – 170 grams) were included in this study. They were divided into four equal groups; each group have six rats: Group I (Normal: control of healthy), group II (STZ: control of diabetes), group III (diabetic group post-treated with MSC.s) and group IV (diabetic group post-treated with MSC.sin combination with vitamin D3). Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg); MSC.s were injected intravenously into the rat tail vein in group III and group IV then left for sixweeks; vitamin D (cholecalciferol) was administered orally at 150 ng (500 IU/kg) each other day at three times per week for a long 6 weeks.Blood glucose leveland body weight were measured weekly for all groups at the beginning of the study at the intervalsixweeks. While, haematological parameters were measured after six weeks. Results: Diabetic group (group II) showed significant higher glucose levels while there was a significant lower body weight levels compared to control of non-diabetic group. Group IIIas well as group IV showed significant elevation of body weightand reduction of blood glucose level as well as amelioration of haematological parameters in compared to group II.Conclusion: treatment with MSC.sand/or in combination with vitamin D3 showed significant lower levels of glucose and higher body weight levels as compared to diabetic group.