Atrial natriuretic peptide (ANP) is a hormone released predominantly by atrial myocytes in response to atrial wall stretch. Levels of plasma ANP are increased during experimental hypoxia and in various disease states including coronary heart failure, myocardial infarction and diabetes (Sahai & Ganguly, 1992). The distribution of ANP and its effects on contraction and intracellular Ca²⁺ in ventricular myocytes from streptozotocin (STZ)-induced diabetic rat have been investigated. Diabetes was induced in male Wistar rats (220-250 g) by a single ip. injection of STZ (60 mg/kg body weight). Experiments were performed 8-12 weeks later after STZ treatment. Animals were killed humanely. Blood glucose in STZ-treated rats was 347.4 ± 15.2 mg/dl compared to 68.0 ± 2.3 mg/dl in age-matched controls (n=5). Immunoconfocal techniques were used to measure the distribution of ANP. STZ treatment significantly increased the number of myocytes immunolabeled with antibodies against ANP. The percentage of ANP(+) and ANP(-) labelled myocytes from control rat were 16.8 ± 5.3 % and 83.1 ± 5.3 % (n=67), respectively. However, the percentage of ANP(+) and ANP(-) labelled myocytes from STZ-treated rats were 52.1 ± 7.2 and 53.2 ± 4.6 % (n=67), respectively. Shortening was measured in electrically stimulated (1 Hz) myocytes superfused with normal Tyrode solution containing 1 mM Ca²⁺ at room temperature with a video edge detection system (VED-114, Crystal Biotech, USA). Time to peak (TPK) shortening was significantly prolonged in myocytes from STZ-treated (360 ± 5 ms, n=19) compared to controls (305 ± 5 ms, n=27). Amplitude of shortening was marginally increased in myocytes from STZ-treated rat and treatment of myocytes with 1×10^-7 M ANP for 1 h produced a small reduction in amplitude of shortening in myocytes from both STZ-treated and control rats. Intracellular [Ca²⁺] was measured in fura-2/AM loaded myocytes. The amplitude of the Ca²⁺ transient was significantly increased in myocytes from STZ-treated rats (0.39 ± 0.02, n=20 fura-2 ratio units) compared to controls (0.29 ± 0.02, n=26 fura-2 ratio units) and treatment with ANP reduced the amplitude to control levels. Our results show that the distribution and level of ANP is upregulated in diabetic rats and that ANP may have a Ca²⁺ modulatory role in ventricular myocytes from STZ-induced diabetic rat. Data are means ± S.E.M. Statistical comparisons were made using independent sample t test or ANOVA followed by Bonferroni corrected t test for multiple comparisons, as appropriate. P values less than 0.05 were considered significant. Ethical clearance obtained from the Faculty of Medicine & Health Sciences Ethics Committee, United Arab Emirates University.