Abstract: Adult human’s failure of cardiac regeneration after cardiac injury is the main cause of heart failure. For all the lack of significant cardiac regeneration in all adult mammals, some vertebrates can regenerate myocardium throughout their life. Recent studies have indicated that mammals have cardiac regeneration potential during development and perinatal period. In a variety of animal models, the mechanisms of heart regeneration are similar, such as inflammatory response, matrix deposition and remodeling, and cardiomyocyte proliferation. Understanding why extensive scar forms and regeneration fails after adult mammalian cardiac damage may provide a new therapeutic strategy for heart failure.