Sodium-dependent-glucose-transporter 2 (SGLT2) inhibitors are a novel therapy for type 2 diabetes. They block glucose reabsorption by the kidney which promotes urinary glucose excretion and lowers blood glucose levels. We aimed to determine whether SGLT2 inhibition prevents or improves kidney disease in diabetes. Male db/db and db/m (C57BLKS/J) mice were administered with once-daily oral treatment of the SGLT2 inhibitor, empagliflozin (10mg/kg/day), or vehicle from 10-20 weeks of age (n=10/group). These were compared with db/db mice which received metformin (250mg/kg/day) or empagliflozin + metformin co-therapy (dose as per single). In the last week of treatment, vehicle-treated db/db mice had higher fasting plasma glucose and HbA1c levels, and impaired glucose tolerance (OGTT) compared to non-diabetic db/m (P<0.05). Empagliflozin monotherapy reduced fasting plasma glucose and HbA1c levels, and provided some benefits for the glucose and insulin  profiles during the OGTT compared to vehicle treated db/db mice (P<0.05), while metformin had no significant effects. Combination therapy reduced fasting plasma glucose and HbA1c and, during the OGTT, lowered blood glucose (AUC_glucose) and increased plasma insulin (AUC_insulin) levels (P<0.05). Glomerular filtration rate, estimated using transcutaneous decay of intravenously injected FITC-labeled sinistrin, and plasma cystatin C levels were not different between groups. However, all db/db mice had albuminuria, increased urinary KIM-1 levels, enlarged kidneys, and glomerulosclerosis (P<0.05), which were unaffected by administered therapies. Despite glycaemic improvements, empagliflozin did not improve kidney disease in this experimental model of diabetes. Hyperglycaemia prior to the onset of treatment may have been sufficient for disease development. The potential for SGLT2 inhibition to slow progression to more advanced stages of kidney disease remains to be assessed.