This experimental study investigated the impact of hyperglycemic control on left ventricular (LV) function using a model of diabetes mellitus (DM) (induced by streptozocin 60 mg/kg). Sixteen adult-Sprague Dawley rats were divided into group 1 (poor hyperglycemic control, n = 8) and group 2 (good hyperglycemic control, n = 8). Diabetic rats and 8 healthy rats serving as controls (group 3) were sacrificed on day 28 after DM induction. The results demonstrated that HbA(1C) on day 28 was higher in group 1 than in groups 2 and 3 (P < 0.0001). The mRNA expressions of MMP-9 and endothelin-1 were elevated in group 1 compared with that in groups 2 and 3 (P < 0.05), whereas PGC-1alpha and eNOS were lower in group 1 than in groups 2 and 3 (P < 0.05). The number of apoptotic nuclei was higher in group 1 than in groups 2 and 3 (P < 0.01). The integrated area (microm(2)) of connexin43 (Cx43), Cx43 protein expression, and LV function were lower in group 1 than in groups 2 and 3 (P < 0.05). Moreover, PKC-epsilon expression in the mitochondrial compartment was decreased in group 1 compared to that in groups 2 and 3 (P < 0.005).