Type 2 Diabetes is an enormous health burden affecting 350 million people worldwide. Loss of b cell mass is a feature of the disease, and evidence suggests that this is the result of apoptosis. We were the first to identify that the pro-apoptotic Bcl-2 homology domain 3 (BH3)-only molecules Bim is required for glucose-induced apoptosis of islet cells. High concentrations of glucose induce ER and oxidative stress, which result in islet cell death mediated by Bim. Islets isolated from organ donors with type 2 diabetes had increased expression of Bim compared with non-diabetic donors, suggesting Bim is also important in loss of b cells in humans. To determine whether Bim deficiency protects b cells from apoptosis in type 2 diabetes, we crossed Bim-deficient mice with leptin receptor mutant Leprdb/dbmice. These mice were significantly protected from development of hyperglycaemia. We also observed a striking increase in islet size in Bim-deficient Leprdb/dbmice. To quantify this increase in islet mass, we performed optical projection tomography, 3-dimensional imaging of whole pancreas stained with anti-insulin antibodies. Data analysis revealed 2-fold increased islet volume in Bim-deficient compared with wild-type Leprdb/dbmice. There was no difference in islet cell proliferation between wild type and Bim-deficient mice, measured by BrdU uptake. Further studies will determine whether apoptosis is reduced in Bim-deficient islets. Bim is ubiquitously expressed and may be important in many cell types involved in type 2 diabetes pathogenesis, including b cells, the immune system and insulin-sensitive peripheral tissues. Our data suggest that Bim has a direct role in the loss of islet mass in type 2 diabetes. Future studies will determine whether specific deletion of Bim in b cells only also produces the same phenotype.