Physical exercise continues to be a cost-effective strategy to help in slowing the progression of diabetes-induced cardiovascular complications. However, the molecular mechanisms by which regular exercise can improve cardiac function in type 2 diabetes (T2DM) remain poorly characterised. This study investigated the physiological and molecular changes that arise in hearts of 10-11 month old Goto-Kakizaki (GK) type 2 diabetic rats following 2-3 months of daily treadmill exercise compared to sedentary counterparts. Shortening and intracellular [Ca2+]i transients were measured in ventricular myocytes with video edge detection and fluorescence photometry, respectively. Structure and gene expression were assessed in ventricular tissue with electron microscopy, immunohistochemistry and real-time RT-PCR. Ethical clearance for the project was obtained from the College of Medicine and Health Sciences, UAE University and the University of Central Lancashire Exercise training in GK rats significantly (mean±SEM; p<0.05; ANOVA; n=15-18) reduced blood glucose level (133.07±9.79 mg/dl vs161.29±12.77 mg/dl) and body weight (418.93± 6.80 g 443.64±7.94 g vs) and increased heart weight (1.64±0.03 g vs 1.60±0.04 vs) and heart weight to body weight ratio (0.392±0.013 vs 0.361±0.008) compared to sedentary GK animals. The amplitude of shortening decreased slightly in ventricular myocytes from exercised GK compared to sedentary GK rats. However, the amplitude of [Ca2+]i transients increased in ventricular myocytes from exercised GK compared to sedentary GK rats. LV from sedentary GK rats displayed disorganised architecture which was characterised by hypertrophied cardiomyocytes, disarray of myofibres and irregular myofibril pattern compared to exercised GK animals. Exercise training in GK rats significantly (p<0.05) reduced interstitial fibrosis, caspase-3- mediated apoptosis, ANP, BNP, TGFβ1, and gene expression of extracellular matrix components and regulators associated with cardiac fibrosis compared to sedentary GK animals. Moreover, exercise training significantly (p<0.05) increased the expression of genes encoding sodium-calcium exchanger, phospholamban and Calmodulin2 (CALM2), but not SERCA2a, ryanodine receptor, Cav1.2, Cav1.3 and CaMKd compared to sedentary GK rats. It is concluded that exercise training can reduce blood glucose concentration, thereby improving the integrity of the myocardium against diabetes.