The use of small and large animal models is vital in the clinical translation of experimental data in cardiovascular research. Thymosin beta 4 is a peptide which has shown good cardioprotective potential in several in vitro and animal experiments. The peptide increases cell survival, angiogenesis and progenitor cell migration while it reduces inflammation and cell death. In small animal models for myocardial infarction it limits infarct size and improves cardiac function. It has also shown promising effect in pig models for myocardial injury. In this thesis, we aimed to determine the effect of the peptide in mouse models for myocardial infarction and anthracycline-induced cardiomyopathy and in a pig model for global ischemia-reperfusion injury. We focused on improvement in cardiac functional outcome by performing echocardiography, magnetic resonance and positron emission tomography imaging. The underlying mechanism were investigated by measuring cell death, inflammation and gene-expression analysis. After myocardial infarction thymosin beta 4 treatment may have reduced infarct expansion and left ventricle remodeling with improvement in left ventricle function. Treatment was associated with upregulation of chitinase 3-like-1, a novel protein involved in fibrosis and inflammation. We also observed increased activity of the cardioprotective enzyme CD73. Anthracycline caused high mortality with limited change in cardiac contractility and was therefore not considered suitable for inducing experimental cardiac dysfunction. Thymosin beta 4 did not attenuate global myocardial ischemia-reperfusion injury nor did it influence myocardial cell death or inflammation. The cardioprotective effect seen in mice could not be demonstrated in pigs and further therapeutic evaluation is therefore needed.