The aim of the present study was to investigate the effects of microRNA (miR)-128 inhibition on the targeted activation of peroxisome proliferator-activated receptor gamma (PPARG) and on cardiomyocyte apoptosis induced by myocardial ischemia/reperfusion (I/R) injury. In vitro, the expression of PPARG was detected by reverse transcription-quantitative polymerase chain reaction and western blotting in neonatal rat ventricular myocytes (NRVMs) and HEK293 cells transfected with the mimics or inhibitors of miR‑128 or control RNA. Luciferase reporter assays were used to identify whether PPARG is a direct target of miR‑128. In vivo, miR‑128 was knocked down via ear vein injection of antagomir‑128 in a rabbit myocardial I/R injury model. Western blotting investigated the activation of Akt [phosphorylated (p)‑Akt] and the expression of total‑Akt, PPARG and myeloid leukemia cell differentiation protein‑1 (Mcl‑1) in the myocardium. Cardiomyocyte apoptosis was examined with transmission electron microscropy and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. PPARG mRNA and protein were downregulated in NRVMs transfected with miR‑128 mimics, but upregulated by antagomir‑128 compared with control. This indicates that PPARG is a direct miR‑128 target. Activation of Akt (p‑Akt), Mcl‑1 and PPARG expression in the myocardium were increased by miR‑128 inhibition. Furthermore, miR‑128 antagomirs significantly reduced apoptosis in hearts subjected to I/R injury, which was blocked by the PPARG inhibitor GW9662. In conclusion, miR‑128 inhibition attenuated I/R injury‑induced cardiomyocyte apoptosis by the targeted activation of PPARG signaling.