OBJECTIVE: To evaluate the effect of Nelumbo Nucifera leaf water extract (NNLE) on insulinoma (RIN) cells induced by interleukin-1 beta (IL-1 beta) and interferon -g (IFN-gamma), and injured pancreatic (beta-cells induced by Streptozotocin (STZ) in rats. METHODS: The anti-oxidative effects of NNLE were assessed using 1,1-diphenyl-2-picryl hydrazyl (DPPH) and nitric oxide (NO) scavenging assays. The inhibitory effect of NNLE on alpha-glucosidase and DPP (dipeptidyl peptidase)-IV was measured in vitro. Pancreatic beta-cell protective and insulin secretory effects were assessed, using IL -1 beta and IFN-gamma-induced rat RIN cells. STZ-induced diabetic rats were treated with 50, 100, and 400 mg/kg NNLE for 4 weeks. The effects of NNLE on blood glucose (BG), body weight (BW), and lipid profiles were measured. RESULTS: NNLE inhibited DPPH, NO, alpha-glucosidase, and DPP-IV which were directly linked to the function of beta-cells. Furthermore, NNLE protected RIN cells from toxicity induced by IL-1 beta and IFN-gamma, decreased NO production, and increased insulin secretion. NNLE caused a significant reduction in blood glucose, triglyceride (TG), total cholesterol (TC), blood urea nitrogen (BUN), and creatinine in STZ-induced diabetic rats. Furthermore, it significantly decreased BW loss in STZ-induced diabetic rats. CONCLUSION: Our results suggest that NNLE reduced the toxicity in insulinoma cells and increased insulin secretion in pancreatic beta-cells in STZ-induced diabetic rats. (C) 2016 JTCM. All rights reserved.