To study the effects of high fat diet on the proliferation, differentiation and collagen synthesis of mouse cardiac fibroblasts through exosomes from small intestinal epithelium. Methods: Exosomes from small intestinal epithelium of normal/ high fat diet mice were extracted and co-cultured with primary mouse cardiac fibroblasts. Exosomes uptake of cardiac fibroblasts of the two groups was observed by PKH26 labeling, and the gene expressions of proliferation, gmjydifferentiation, fibrosis and inflammation of cardiac fibroblasts were observed by fluorescence quantitative PCR. Immunofluorescence staining was used to observe the expression of α-SMA, Col1a1 and Col3a1 in cardiac fibroblasts of the two groups. Results: The exosomes from small intestinal epithelium of normal / high-fat diet mice could be absorbed by cardiac fibroblasts, and there was no difference in uptake efficiency between them. Compared with the normal diet group, that of mice fed with high fat diet could significantly increase the gene expression of cardiac fibroblasts, such as proliferation, differentiation, extracellular matrix accumulation, inflammation, and enhance the ability to synthesize α-SMA, Col1a1 and Col3a1 protein. Conclusion: High fat diet can promote the proliferation, differentiation and collagen production of cardiac fibroblasts through exosomes from small intestinal epithelium.