〔Abstract〕 Objective The purpose of this study was to investigate the effects of plasma exosome-derived miR-29b-3p in myocardial ischemia-reperfusion injury(MIRI) rats on hypoxia/reoxygenation(H/R) cardiomyocyte after sevoflurane(SEV) postconditioning through targeting IGF1. Methods The GEO database was used to screen differentially expressed miRNAs in MIRI, and cardiomyocytes were treated with H/R to construct a MIRI cell model. The expression of miR-29b-3p and IGF1 in the MIRI cell model post-treated with SEV was intervened, and then the survival rate of cardiomyocytes was detected by MTT, apoptosis was detected by flow cytometry, and inflammatory factors(IL-1β and TNF-α) in cardiomyocytes in each group were detected by ELISA. Results Compared with Normal group, the expression of miR-29b-3p in plasma exosomes of MIRI rats was enhanced(P<0.05), and the target-binding relationship between miR-29b-3p and IGF1 was confirmed(P<0.05). After SEV post-treatment, the expression of miR-29b-3p in H/R-stimulated cardiomyocytes decreased, while the expression of IGF1 increased(both P<0.05). Overexpression of miR-29b-3p in plasma exosomes could significantly inhibit the survival rate of H/R cells after SEV treatment, aggravate apoptosis and inflammatory response, while knockdown of miR-29b-3p showed a opposite effects(all P<0.05). The rescue experimental data showed that overexpression of IGF1 could partially reverse the effects of overexpression of miR-29b-3p on H/R cell injury after SEV treatment(all P<0.05). Conclusion Plasma exosome-derived miR-29b-3p promotes H/R cardiomyocyte injury after SEV treatment by targeting IGF1.