Previous in vivo biotelemetry studies have demonstrated reductions in heart rate and heart rate variability in the strepozotocin (STZ)–induced diabetic rat (Howarth et al. 2005). These heart rhythm disturbances may be attributed to extrinsic defects in autonomic control and/or intrinsic defects in the conduction system of the heart. We have investigated the effects of STZ–induced diabetes on intrinsic heart rhythm. Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) administered to young male Wistar rats (200-250g). Experiments were performed 8-10 weeks after STZ treatment. In some experiments spontaneous heart rates were recorded in Langendorf perfused (8 ml/g heart/min) hearts perfused with a normal Tyrode solution containing 1.8 mM Ca²⁺ maintained at 35-37°C. In other experiments an isolated sinoatrial node (SAN) preparation containing the SAN and part of the right atrium was dissected. The preparation was then placed in a tissue bath and superfused at 4 ml/min with normal Tyrode solution at 35±0.5°C. Extracellular potentials (ECPs) were recorded by two bipolar electrodes from the isolated SAN preparations as described by Lei et al. (2004). Electrodes were placed in the centre of the sinoatrial node and in the neighbouring atrial muscle in the right atrial appendage. Data are expressed as means ± S.E.M. (with number of preparations). Statistical comparisons were made with Independent samples t test with a P value of <0.05 considered significant. Diabetes was confirmed by a significant elevation of blood glucose (365±33 mg/dl, n=7) compared to age-matched controls (66±4 mg/dl, n=7) and a reduced body weight gain in diabetic rats (235±9 g, n=7) compared to controls (352±9 g, n=7). Heart rate recorded in Langendorff perfused hearts was significantly lower in diabetic rats 171±12 bpm (n=6) compared to 229±9 bpm (n=6) in controls. The pacemaker cycle length and the sino-atrial conduction time were significantly prolonged in diabetic SAN preparations (415.2±42.6 and 12.3±1.8 ms, n=6) compared to controls (255.2±6.7 and 7.4±0.6 ms, n=6). Heart rhythm defects in the STZ-induced diabetic rat might be partly attributed to intrinsic defects in sinus rhythm generation and conduction between the SAN and neighbouring atrium.