Diabetic nephropathy (DN), is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The factors and mechanisms that contribute to progression of DN are still undefined. To address the contribution of B2-kinin receptors (B2KR) to the development of DN, we studied B2KR knockout mice (B2KR^-/-) and their wild type littermates (B2KR^+/+). Diabetes was induced by daily intraperitoneal injection of STZ (50mg/kg body weight) for 3-5 days. We used a total of 48 mice divided into 4 groups, 12 mice in each group. Group 1, wild type non-diabetic-controls (B2KR^+/+ C); group 2, wild type-diabetic (B2KR^+/+ D); group 3, B2KR knockout-control (B2KR^-/- C) and group 4, B2KR knockout-diabetic (B2KR^-/- D). Glucose levels and albumin excretion rate (AER) were measured at predetermined intervals. Half of the mice were sacrificed at 3 months and the remaining half at 6 months. Plasma glucose levels were markedly elevated in both B2KR^+/+ D and B2KR^-/- D groups of mice compared to their non-diabetic controls. Diabetic B2KR-/- mice display reduced AER, as well as reduced glomerular and tubular injury compared to diabetic B2KR+/+ mice. The renoprotection conferred by deletion of B2KR was associated with increased renal expression of B₁-kinin receptors (B1KR) and angiotensin II AT₂ receptors and decreased expression of the prosclerotic connective tissue growth factor (CTGF). At a cellular level, our findings demonstrate that bradykinin (BK) down regulates the expression of AT₂ receptors in mesangial cells (MC). These findings provide the first evidence that targeted deletion of B2KR protects against the development of DN.