Diastolic dysfunction is an increasingly recognised complication of diabetes that develops in relatively young patients as a result of diabetic cardiomyopathy (DCM). With recent advances in echocardiographic technology now permitting the reliable assessment of diastolic function the rat, we examined cardiac function and structure in diabetic rodents and assessed the effects of intervening with tranilast, an anti-fibrotic compound that has been shown to attenuate the actions of transforming growth factor- (TGF-) in cardiac fibroblasts. We also sought to examine the mechanism whereby tranilast inhibits the actions of TGF-. Six week old heterozygous (mRen-2)27 rats were randomized to receive either streptozotocin or citrate buffer then further randomized to receive either tranilast (400 mg/kg/day by twice daily gavage) or vehicle for another eight weeks. Cell signalling was examined in neonatal cardiac fibroblasts. After 8 weeks diabetic rats showed evidence of impaired diastolic function with reduced E/A ratio and prolonged deceleration time in association with fibrosis, apoptosis and hypertrophy (all p<0.05). Treatment with tranilast prevented the development of diastolic dysfunction and the histopathological features of DCM. While tranilast did not affect Smad phosphorylation it significantly attenuated TGF- induced p44/42 mitogen activated protein kinase (MAPK) phosphorylation.