Type 2 diabetes mellitus (DM) affects a large population worldwide. DM is often considered as a syndrome of disordered glucose metabolism. Current conventional drug therapies for DM are usually insufficient and medicinal herbs with antihyperglycemic activities are increasingly sought by diabetic patients and health care professionals. Nerium Oleander (N.O.) is known to be effective in lowering of postprandial blood glucose in DM patients as a folk remedy. In this study we aimed to evaluate effect of N.O. distillate in glucose uptake activity of hepatocytes and adipocytes. The human hepatoma cells Hep3B and mouse adipocyte 3T3-L1 cells were cultured. Depending on the groups, different concentrations insulin (1, 10, 20 IU/ml) and N.O. (0.1, 1, 10, 50 μg/ml) were added to medium for 48 h. Cellular toxicity and proliferation were evaluated by LDH secretion levels and MTT test. A metabolizable fluorescent derivative of glucose, 2-NBDG and FITC-insulin were used for glucose uptake and insulin binding activity. Insulin increased cellular proliferation and decreased LDH leakage and apoptosis in both cell types. Lower dosages of N.O. has no significant effect on apoptosis and cell number while at the highest dosages minimal cytotoxicity was seen mainly in adipocytes. Main effect of N.O. treatment was increased glucose uptake in Hep3B and 3T3-L1 cells (P<0.001). Our results showed that N.O. may be offered as new approaches to treatment of type 2 diabetes by modulating cellular glucose uptake.