Cardiovascular disease is the leading causes of death worldwide with ischemic heart disease (IHD) the largest contributor. As an imbalance in oxygen supply and demand, ischemic damage can be minimised by timely reperfusion, however reperfusion itself can also result in further damage. Individuals with diabetes are at a greater risk of developing IHD with higher mortality rate and poorer outcomes following an ischemic event. The current study utilises a rat model of type 2 diabetes (T2D) to investigate how the heart recovers after an ischemic event by profiling the changes of protein phosphorylation and metabolite abundance in physiological and T2D conditions. Rat hearts were subjected to Langendorff perfusion to produce increasing periods of reperfusion, up to 60 min (60R) after 15 min of global ischemia (15I). Phosphoproteomic analysis was conducted using isobaric tags across the reperfusion time course, prior to mass spectrometry (MS) while metabolomics was performed using a targeted MS approach. Significant changes in abundance were identified in >8000 phosphopeptides and 112 metabolites across the time course, with a majority significantly altered within the first 5 minutes reperfusion (>75% for phosphopeptide, >65% for metabolites). Differential analysis between the diabetic and non-diabetic hearts revealed altered regulation of a number of kinases including CaMK2, FAK, PI3K, MAP2K2 and associated pathways, which all have a role in healthy heart function. This was confirmed using metabolomics which showed that high energy phosphates were being differentially utilised. By elucidating the differences in signalling pathways and kinase modulators between diabetic and non-diabetic hearts during reperfusion, novel therapeutic targets are possible to improve cardiovascular outcomes for diabetics after an ischemic event.