Elderly patients face the problems of morbidity and mortality due to age-mediated disabilities. The purpose of the present study was to investigate the expression of thrombospondin-1 (TSP-1) and transforming growth factor-β (TGF-β) in aging mice, and its probable mechanism in the pathological changes of aging myocardium. The aging model group (AM) comprised 30-month-old mice, while the control group comprised 2-month-old mice. The pathological changes were explored by H&E staining, and the contents of superoxide dismulase (SOD) and malondialdehyde (MDA) in the hearts were determined by xanthine oxidation or TBA colorimetry. TSP-1 and TGF-β expression in the left ventricular myocardium was also measured by immunohistochemistry. The results showed that the activities of SOD decreased and the MDA content increased markedly in the hearts of the AM group compared to the control group. H&E staining showed that the control group myocardial cells lined up in order with clear structure and stained equably, while the AM group myocardial cells lined up in disorder with an augmented cell body and the appearance of many granules and interstitial fibrosis. Compared to the control group, in the hearts of the AM group, TSP-1 and TGF-β protein expression in myocardial cells showed a significant increase (P<0.01). TSP-1 and TGF-β expression increased in the myocardium, which may be related to pathological changes of age-related heart diseases, such as hypertrophy, fibrosis of myocardial cells and microvessel dissepiment thickening.