Aldosterone (Aldo) is recognized as an important risk factor for cardiovascular diseases. IL-18 induces myocardial hypertrophy, loss of contractility of cardiomyocytes and apotosis leading myocardial dysfunction. However, so far, there have been few reports concerning the interaction between Aldo and IL-18. The present study examined the effects and mechanisms of Aldo on IL-18 expression and the roles of Peroxisome proliferator-activated receptors (PPAR) agonists in rat cardiomyocytes. We used cultured rat neonatal cardiomyocytes stimulated with Aldo in order to measure IL-18 mRNA and protein expression, and Rho-kinase and NF-kB activity. We also investigated the effects of PPAR agonists on these actions. Aldo, endothelin-1 (ET-1), and angiotensin-II (Ang-II) increased IL-18 mRNA and protein expression. Mineralocorticoid receptor antagonists, endothelin A receptor antagonist, and angiotensin-II receptor antagonist inhibited Aldo-induced IL-18 expression. Aldo induced ET-1 and Ang-II production in cultured media. Moreover, Rho/Rho-kinase inhibitor and statin inhibited Aldo-induced IL-18 expression. On the other hand, Aldo up-regulated the activities of Rho-kinase and NF-kB. PPAR agonists attenuated the Aldo-induced IL-18 expression and NF-kB activity but not the Rho-kinase activity. Our findings indicate that Aldo induces IL-18 expression through a mechanism that involves, at a minimum, ET-1 and Ang-II acting via the Rho/Rho-kinase and PPAR/NF-kB pathway. The induction of IL-18 in cardiomyocytes by Aldo, ET-1, and Ang-II, might therefore cause a deterioration of the cardiac function in an autocrine and paracrine fashion. The inhibition of the IL-18 expression by PPAR agonists might be one of the mechanisms whereby the beneficial cardiovascular effects are exerted.