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This study aimed to assess impact of high fat diet (HFD) on cardiac apoptosis, and cardiac uncoupling proteins (UCPs) 2&3 expression. Twenty rats were fed either (45%) or (10%) fat diet for 6 months, then cardiac tissue expression of BAX, Bcl2, Fas, Fas-L (markers for apoptotic pathways) and UCP 2&3 were assessed. Results revealed enhancement of intrinsic and extrinsic cardiomyocyte apoptosis cascades in the myocardial tissue of HFD fed rats and down regulation of UCP2 and up regulation of UCP3 gene expression at 6 months. The present work highlights novel role for the uncoupling proteins in the experimental model of HFD feeding.