Abstract: AIM:To observe the effect of cannabinoid receptor II (CB2) activation on cardiac stem/progenitor cell proliferation in mice myocardial infarction (MI) models. METHODS: C57BL/6 male mice were randomly allocated into four groups: Sham group (Sham), MI group (MI), MI+CB2 agonist AM1241 group (MI+AM1241), and MI+CB2 agonist AM1241+CB2 antagonist AM630 group (MI+AM1241+AM630). Mice MI model was induced by ligation of the left anterior descending artery. Echocardiography was performed to evaluate left ventricular ejection fraction (LVEF). The number of cardiac stem/progenitor cells was observed with immunostaining for cardiac stem/progenitor cell surface markers c-kit and Sca-1 in peri-infarction region at day 7 post MI. Real-time PCR analysis was conducted to examine the expression of c-kit, Sca-1 and MDR1 in the border zone of infarcted myocardium at day 7 and 14 post-MI. RESULTS: Echocardiography revealed that AM1241 ameliorated LVEF compared with that in MI group at day 7 (P<0.01) and day 14 (P<0.01) post-MI. Both immunofluorescence staining and RT-PCR demonstrated that the administration of AM1241 significantly increased the expression of c-kit and Sca-1 in the border zone of infarcted myocardium (P<0.05) and the protective effect of AM1241 on the infarcted myocardium was inhibited by CB2 antagonist AM630. CONCLUSION: CB2 receptor activation may promote cardiac stem/progenitor cell proliferation and improve cardiac systolic function.