Membrane NA+/H+ exchanger regulates cell pH, volume, and growth. Abnormal activities have been reported in essential hypertension and type I insulin-dependent diabetes mellitus (IDDM). The aim of this study was to analyze the relationship between erythrocyte NA+/H+ antiport activity and myocardial anatomical and functional parameters in normotensive type I insulin-dependent diabetic patients. We evaluated 26 insulin-dependent diabetic patients (20 normo- and 6 microalbuminuric) and 17 age- and sex-matched healthy controls. Plasma and urine analytes as well as erythrocyte NA+/H+ antiport rate were measured. M-Mode- and 2D echocardiograms with Doppler analysis were performed in all subjects. Diabetic people, both normo- and microalbuminuric, had a Na+/H+ antiport activity significantly higher than control subjects (p < 0.01). All echocardiographic parameters relative to left ventricular volume, cardiac mass and systolic function overlapped in the study groups. Of Doppler indexes, evaluating the left ventricular diastolic filling, the late peak flow velocity (peak A) was significantly higher in diabetic patients (p < 0.01). E/A ratio was heightened in the control group compared to diabetics, as a whole as well separately considered (p < 0.01). Antiport significantly correlated with PWTh, STh, E/A, UAER, serum sodium, and gender (p < 0.0001). The linear and significant correlation found between Na+/H+ exchange and some cardiac indexes suggest the increased Na+/H+ antiport activity as possible predictive risk factor for the development of diabetic cardiomyopathy.