Recent study suggests that exogenous ghrelin administration might decrease renal sympathetic nerve activity in conscious rabbits. In the present study, we investigated whether ghrelin administration would attenuate left ventricular (LV) remodeling following myocardial infarction (MI) via the suppression of cardiac sympathetic activity. Ghrelin (100µg/kg SC twice daily, n=15) or saline (n=15) were administered for 2 weeks from the day after MI operation in Sprague-Dawley rats. The effects of ghrelin on cardiac remodeling were evaluated by echocardiographic, hemodynamic, histopathologic, and gene analysis. In addition, before and after ghrelin (100µg/kg SC, n=6) was administered in conscious rats with MI, the autonomic nervous function was investigated by power spectral analysis obtained by a telemetry system. In ghrelin-treated rats, LV enlargement induced by MI was significantly attenuated compared to saline-treated rats. In addition, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt max/min in ghrelin-treated MI rats compared to saline-treated MI rats. Furthermore, ghrelin attenuated an increase in morphometrical collagen volume fraction in the non-infarct region, which was accompanied by the suppression of collagen I and III mRNA levels. Importantly, 2-week administration of ghrelin dramatically suppressed the MI-induced increase in heart rate and plasma noradrenaline concentration to the similar levels as in sham-operated controls. Moreover, acute administration of ghrelin to MI rats decreased the ratio of the low-to-high frequency spectra of heart rate variability (p<0.01). In conclusion, these data suggest the potential usefulness of ghrelin as a new cardioprotective hormone early after MI.