Type 2 diabetes mellitus (T2DM) is present in 25% of patients with atrial fibrillation (AF), the most prevalent arrhythmia in the world. This concomitant disorder enhances thromboembolic events, length of hospital stay after AF ablation, renal impairment after anticoagulation, heart rate variability after glucose-lowering treatment, and cardiac mortality. These patients accumulate inflamed epicardial fat (EAT) with paracrine consequences on β-oxidation of mitochondria, cytosolic Ca fluxes, and sarcomere shortening. Knowing these specific targets will improve the efficacy of personalised preventive and curative therapies since AF leads to AF and EAT accumulation. This review tries to clarify the interplay among epicardial fat accumulation and macrophages with concomitant T2DM and AF to provide a summary of current known mechanisms and therapeutic strategies.