<p>Diabetes mellitus exacerbates cerebral ischemic damage by potentiating neuroinflammation. We hypothesized that activation of the bradykinin type 2 receptor, a mediator of inflammation and vascular dynamics, might be detrimental to ischemic injury development in diabetic animals. We monitored the acute phase of cerebral ischemia in type 1 diabetic mice, diabetic bradykinin type 2 receptor knock-out mice, and their non-diabetic controls using neurological assessment, magnetic resonance imaging, and a comprehensive immuno-histochemical and morphological analysis to quantify changes in microglial, neutrophil, and neuronal populations. Our findings reveal that bradykinin type 2 receptor deficiency ameliorates neurological deficit in non-diabetic mice, despite similar ischemic lesion volumes across all investigated groups. Furthermore, in non-diabetic animals, the bradykinin type 2 receptor plays a discernible role in edema resolution, neuroprotection, and regulation of microglial response to ischemia. However, diabetes, as a stroke comorbidity, alters the involvement of the bradykinin type 2 receptor in ischemic injury development. Bradykinin type 2 receptor-deficient diabetic animals demonstrate delayed microglial cell loss and reduced microglial reactivity following ischemia compared to diabetic animals with functional bradykinin type 2 receptors. The attenuated immune response is accompanied by a marked absence of infiltrating neutrophils within the ischemic territory and improved neuronal survival. This study demonstrates that diabetes profoundly modifies the role of bradykinin type 2 receptor in cerebral ischemic injury, influencing both acute neuroinflammation and cell survival. These findings support the potential of the bradykinin type 2 receptor as a therapeutic target for stroke in diabetic population, warranting further investigation.</p> Graphical Abstract <p></p>