Abstract: AIM: To study the effects of glucagon-like peptide-1 (GLP-1) on the injury of neonatal mice cardiomyocytes induced by hypoxia-reoxygenation (H/R) and to explore the possible mechanism. METHODS: Cultured neonatal mice cardiomyocytes were randomly divided into three groups: normal control group, H/R group, and H/R and GLP-1 group. LDH activity, apoptosis rate of cardiomyocytes and caspase-3 activity were detected. RESULTS: Compared with the normal control group, LDH activity, cardiomyocyte apoptosis rate and caspase-3 activity all increased significantly in the H/R group. Compared with the H/R group, the above three indexes all decreased in the H/R and GLP-1 groups. CONCLUSION: GLP-1 directly acts on cardiomyocytes and protects them from H/R injury mainly by inhibiting apoptosis. GLP-1 may exert its apoptotic effects through regulation of apoptotic or antiapoptotic pathways of caspase-3.