Heart failure is a major cause of premature morbidity and mortality in diabetes mellitus (DM) but the underlying mechanisms are elusive and treatment remains empirical. Previously, we reported that type 2 DM was associated with structural remodelling and associated changes in inflammatory markers of the diabetic heart (D’Souza et al, 2011). The study now investigated the role of hyperglycaemia on cardiomyocyte contractile function and histopathological changes in the left ventricle (LV) of streptozotocin (STZ)-treated type 1 diabetic male Wistar rats compared to age-matched controls, 6-7 weeks after STZ-administration (60 mg/kg body weight) via single intraperitoneal injection, according to Home Office regulation. Contraction and intracellular calcium transients [Ca2+]i were measured in electrically stimulated ventricular myocytes by a video edge detection system and fluorescent method, respectively. Histological and immunohistochemical studies were conducted in small portions of LV tissues stained with Haematoxylin and Eosin, labelled with FITC-conjugated Lectin and the Masson’s trichrome stain for determination of myocyte size and quantitative assessment of fibrosis and caspase-3. STZ-treated rats had significantly (Student’s t-test; p<0.01) higher blood glucose values and reduced heart to body mass ratio relative to controls. Blood glucose levels were 305±7.48 mg/dl and 89.51±3.56 mg/dl and heart to body mass ratios were 0.24±0.11 and 0.31±0.02 for diabetic (n=8) compared to control (n=8) rats. When electrically stimulated at 1 Hz, contractility (% of resting length) was depressed in myocytes from diabetic rats (3.86±0.23%, n=33) compared to controls (5.82±0.34 %, n=33). Myocytes exhibited prolonged time(s) for contraction (129±39 ms (n=19) vs 112.47±5.01 ms (n=16) and relaxation (48.47±2.90 ms (n=19) vs 40.71±2.09 ms (n=16) (p<0.05) in DM compared to controls. Alterations in [Ca2+]i manifested as significant (p<0.05) prolonged time to peak (89.53±2.54 ms, (n=21) vs 77.16±3.5 ms (n=23) ) and prolonged rate of decay ( 0.75±0.02 ms (n=23) vs 0.57±0.02 ms (n=21) of the Ca2+ transient in diabetic myocytes compared to controls. LV morphology was severely altered by DM with significant (p<0.05) increments in fibrous tissue proliferation (3.51±0.44% vs 5.05±0.44%), and smaller myocyte transverse diameter (9.93±0.26 µm vs 9.11±0.25 µm) in diabetic compared to control LV muscle. In STZ-treated LV, the pathology manifested as focal scarring, myofibrillar loss, vacuolisation and large clusters of cells showing histological signs of apoptosis. Activity of cleaved caspase-3 (positive cells/mm2) was also significantly (p<0.01) increased in the STZ-treated group (8.56±0.79) compared to control (1.86±1.30). The results indicate that STZ-induced DM can result in marked histopathological changes that are associated with functional abnormalities of the heart.