In T2D mice, impaired recovery was restored by <i>ARG1</i> ASO or RBCs from <i>ARG1</i> ASO-treated T2D mice.<h4>Conclusions</h4>Arginase 1, but not arginase 2, limits cardiac tolerance to ischemia-reperfusion and contributes to increased vulnerability in T2D. Here, ARG2 is linked to type 2 diabetes mellitus.