Heart failure in diabetes mellitus (DM) is a major cause of premature morbidity and mortality but the underlying mechanisms are elusive and treatment remains empirical. Previously, we reported significant voltage-dependent decreases in force of contraction and L-type calcium current channel activities in the streptozotocin (STZ)-induced diabetic heart. This study now investigated how DM via hyperglycaemia (HG) can induce histopathological changes in the left ventricle (LV) of STZ-treated type 1 diabetic male Wistar rats compared to age-matched controls, six-eight weeks following STZ-administration (60 mg/kg body weight). The study was approved by the Home Office and UCLAN Ethics Committee. A portion of the LV underwent processing for histological studies employing the Haematoxylin and Eosin stain, labelling with FITC-conjugated Lectin and the Masson’s trichrome stain for determination of myocyte size and quantitative assessment of fibrosis, respectively. Immunohistochemical studies were conducted to assess the contribution of diabetes towards activation of apoptotic pathways governed by caspase-3. STZ-treated rats presented with significantly (Student’s t-test; p<0.01) higher blood glucose values (305.86± 7.48 mg/dl, n=6) relative to controls (89.51±3.56 mg/dl, n=6) and significantly (P<0.05) reduced body (232.33±11.07 g) and heart (0.55±0.03 g) weights compared to controls (301.20±16.31 g for body and 0.94±0.05±0.05 g for heart, n=6). Similarly, heart to body mass ratio (g/100 g body weight) was significantly (P<0.05) less in the diabetic animals (0.24± 0.02, n=6) compared to control (0.31± 0.02, n=6). LV morphology was also severely altered by DM. Morphometric analysis indicated significant (P<0.05) increments in fibrous tissue proliferation (5.05±0.44% vs 3.51±0.44%, n=6) and smaller myocyte transverse diameter in the diabetic heart compared to control. The heart was also atrophied and STZ-treated animals presented with lower heart weights and heart weight to body weight ratios relative to controls (p<0.01). In STZ-treated LV, the pathology frequently manifested as focal scarring, myofibrillar loss, vacuolisation and large clusters of cells showing histological signs of apoptosis. Activity of cleaved caspase-3 was also significantly (p<0.01) increased in the STZ-treated group. The results indicate that STZ-induced type-1 DM results in the development of a cardiac disease characterised by LV histopathological changes consistent with a dominant influence of HG and underlying alterations in insulin action.