The study of cardiac progenitor cells (CPCs) is important for understanding the pathogenesis of congenital heart diseases and treating cardiovascular diseases. The mammalian heart is derived from distinct sets of CPCs. T-box transcription factor Tbx18 is expressed in the developing epicardium of the heart and play key roles in heart developing. In order to monitor and elucidate the differentiation potential of Tbx18⁺ CPCs in tissues and living cells, Tbx18 genetic fate-mapping model, Tbx18-Cre/Rosa26R-EYFP and Tbx18-Cre/Rosa26R-LacZ double-heterozygous mice, were founded by Cre-LoxP system. These double-heterozygous mice were useful in monitoring the fate of Tbx18⁺ cells by Cre expression, and tracing the lineage of the cells in embryos and adult mice. YFP⁺ cells can be easily isolated from heart of Tbx18-Cre/Rosa26R-EYFP double-heterozygous mice by fluorescence activated cell sorter(FACS) and be monitored under an inverted confocal microscope. X-gal staining of genetic fate-mapping model revealed that atria, ventricular septum, ventricular wall, coronary vascular and atrioventricular valves can be generated from Tbx18 lineages. Here it was showed that Tbx18⁺ CPCs can differentiate into anticardiac troponin T(cTNT ) positive cardiomyocytes and anti-smooth muscle myosin heavy chain11 positive smooth muscle cells in vivo by immunofluorescence. The heart is a complex organ composed of a diverse set of muscle and non-muscle cells. It was speculated that Tbx18 may play an important role in regulating the signal pathway of progenitor cells differentiating into myogenic cell lineages. These results identify Tbx18 as a marker of cardiac progenitors cells by Tbx18 genetic fate mapping mice, and lay the foundation for researching the differentiation potential of cardiac progenitors into cardiomyocyte lineages in the field of cardiac regeneration and repair.