Objective: To preliminary investigate the effect of plasma exosome and the content microRNA-25-3p (miR-25-3p) on myocardial fibrosis. Methods: The plasma exosomes of 10 healthy C57BL/6 mice (control group) and 10 mice underwent myocardial infarction surgery (group of cardiac fibrosis model) were collected successively. The exosomes were identified by electron microscopy, nano tracking particle analysis and detection of marker protein; qPCR and western blot were used to investigate effects of the two different exosomes on the fibrosis level of mouse cardiac fibroblasts stimulated by angiotensin II (Ang Ⅱ); expression of miR-25-3p in exosomes from two groups were detected by qPCR; western blot and immunofluorescence staining were used to present the effects of miR-25-3p mimic and inhibitor on differentiation and proliferation of cardiac fibroblasts. Results: The plasma exosomes of healthy mice attenuated the increased ?fibrosis level induced by Ang Ⅱ, while the plasma exosomes of myocardial fibrosis model mice lost this function and contained more miR-25-3p; miR-25-3p mimic promoted cardiac fibrosis, while miR-25-3p inhibitor showed the opposite effect. Conclusion：Plasma exosome can protect myocardial fibrosis; the up-regulated miR-25-3p in plasma exosome promotes cardiac fibrosis.