To explore the role of the kallikrein–kinin system in relation to ischemia/reperfusion injury in the kidney, we generated mice lacking both the bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1 −/− / Bdkrb2 −/− ) by deleting the genomic region encoding the two receptors. In 4-month-old mice, blood pressures were not significantly different among B1RB2R-null, B2R-null ( Bdkrb2 −/− ), and WT mice. After 30 min of bilateral renal artery occlusion and 24 h of reperfusion, mortality rates, renal histological and functional changes, 8-hydroxy-2′-deoxyguanosine levels in total DNA, mtDNA deletions, and the number of TUNEL-positive cells in the kidneys increased progressively in the following order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in mRNA levels of TGF-β1, connective tissue growth factor, and endothelin-1 after ischemia/reperfusion injury were also exaggerated in the same order (from lowest to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin receptors play an important role in reducing DNA damage, apoptosis, morphological and functional kidney changes, and mortality during renal ischemia/reperfusion injury.