Objective To investigate the regulation of MAPK signaling pathway mediated by transient receptor potential vanilloid type 1 (TRPV1) on myocardial autophagy in ischemia/reperfusion (I/R) rats and its role in injury repair. Methods Rats were randomly divided into sham operation group, I/R group (model) and I/R+Capsaicin (CS) group, with 8 rats in each group. I/R models were established in other groups except sham operation group. Five minutes before modeling, rats in I/R+CS group were intraperitoneally injected with CS(TRPV1 agonist at a dose of 20 mg/kg). Cardiac function was evaluated by echocardiography. Evans blue (EB)/2,3,5- triphenyltetrazole staining (TTC) was used to estimate the infarct area. Quantitative western blot analysed autophagy and autophagy-related proteins. H9c2 cells were divided into control (Con) group, hypoxia/reoxygenation (H/R) group, H/R+Capsaicin (CS) group and H/R+CS +Anisomycin(p38 agonist) group. The autophagy flux of cells in each group was evaluated by using Machery-GFP-LC3 adenovirus. Results Compared with the sham operation group, the ejection fraction and shortening fraction of I/R group decreased significantly (P＜0.05), and a large area of myocardial infarction occurred (P＜0.05), while the ejection fraction and shortening fraction of I/R+CS group increased significantly (P＜0.05), and the area of myocardial infarction decreased significantly (P＜0.05) Compared with I/R group, the protein expressions of TRPV1, LC3-II/LC3-I, Atg5, Beclin-1 and Rab7 in I/R+CS group were significantly up-regulated to about 3.8 times, 1.6 times, 1.3 times, 1.7 times and 1.9 times (P＜0.05), and the expressions of P62, p-p38/p38 and p-JNK/JNK decreased significantly by 36.1%, 55.9% and 37.4%(P＜0.05) Compared with con group, autophagy and autophagosome in H/R group increased significantly (P＜0.05) Compared with H/R group, autophagy in H/R+CS group increased significantly (P＜0.05) In addition, autophagy in H/R+Anisomycin group was lower than that in H/R+CS group (P＜0.05) Conclusion Capsaicin can enhance autophagy flux through MAPK signaling pathway to reduce myocardial I/R injury, which provides a new insight into the cardioprotective effect of TRPV1