Objective：To explore the potential damage effects and related mechanisms of clozapine（CLP）on the heart development of zebrafish. Method：12.5 μmol/L CLP（L -CLP）and 25.0 μmol/L CLP（H -CLP）were used to culture zebrafish embryos for 72 hours， respectively. The heart morphology，heart rate，and the distance between venous sinus and arterial bulb（SV -BA）were observed under microscope；The expression of cardiac development-related genes NKX2.5，Hand2 and Cmlc2 were detected by fluorescence quantitative PCR；In addition，after 24 hours of culture，the endoplasmic reticulum inhibitor 4-phenylbutyric acid（4-PBA）or dopamine D2 receptor inhibitor bromocriptine（BRC）were added to the H-CLP group for 48 hours. Then，we counted the cardiac function indicators，and detected the expression of endoplasmic reticulum stress genes（Chop、Bip）and apoptosis-related genes（Caspase3，Bax/Bcl2）. Results： CLP induced damages of cardiac structure and function in a dose-dependent manner，induced the expression of Chop and Bip，and further increased the expression of Caspase3 and Bax/Bcl2. 4-PBA and BRC significantly alleviated CLP-induced cardiac injury and decreased the expression levels of Chop、Bip、Caspase -3 and Bax/Bcl2. Conclusion：CLP can damage the heart development of zebrafish，and the mechanism may be related to inhibiting dopamine D2 receptor and stimulating endoplasmic reticulum stress.