OBJECTIVE： To explore the mechanism of differentiation from cardiac stem cells （CSCs） into cardiac cells induced by Cornu Corvi polypeptides. METHODS： CSCs were isolated from SD rats， and cultured to P3 generation after identification and then divided into blank control group， 5-azacitidine induction group （3 μmol/L）， Cornu Corvi polypeptides induction group （800 μg/ml） and combination induction group. Except blank control group was cultured with culture solution containing 3％ FBS， other groups were cultured with culture solution containing relevant derivant for 14 d. The expression of cTnT was determined by immunohistochemical method； the expression of cTnT， ATF-2 and MEF-2C were determined by immunoblot assay； mRNA expression of cTnT， Nkx2.5 and GATA4 were detected by RT-PCR. RESULTS： CSCs were prepared successfully with purity＞97％. Compared with blank control group （cTnT being negative）， cTnT of induction groups were positive， and the protein expression of cTnT， ATF-2 and MEF-2C and mRNA expression of cTnT， Nkx2.5 and GATA4 were all increased （P＜0.05）. Compared with 5-azacitidine induction group， the protein expression of cTnT and MEF-2C and mRNA expression of cTnT and GATA4 were decreased in Cornu Corvi polypeptide groups （P＜0.05）； the protein expression of cTnT， ATF-2 and MEF-2C and mRNA expression of cTnT and GATA4 were all increased in combination induction group （P＜0.05）. CONCLUSIONS： Cornu Corvi polypeptides can induce differentiation of CSCs into cardiac cells by promoting the expression of Nkx2.5， GATA4， ATF-2， MEF-2C and other transcription factors.