Cardiovascular complications account for significant morbidity and mortality in the diabetic population. Diabetic cardiomyopathy (DCM), a prominent cardiovascular complication, has been recognized as a microvascular disease that may lead to heart failure. During the past few decades, research progress has been made in investigating the pathophysiology of the disease; however, the exact molecular mechanism has not been elucidated, making therapeutic a difficult task. In this review article, we have discussed a number of diabetes-induced metabolites such as glucose, advanced glycation end products, protein kinase C, free fatty acid and oxidative stress and other related factors that are implicated in the pathophysiology of the DCM. An understanding of the biochemical and molecular changes especially early in the DCM may lead to new and effective therapies toward prevention and amelioration of DCM, which is important for the millions of individuals who already have or are likely to develop the disease before a cure becomes available. (C) 2012 Elsevier Inc. All rights reserved.