Purpose: These experiments aimed to analyze the effects of genistein and/or exercise on the expression of miRNA-133, IGF-1, and Bcl-2, Bax plus oxidative stress and inflammation markers in the heart of diabetic ovariectomized rats. Methods: Animals were divided into seven groups (n=8): control, sham, ovariectomy (OVX), diabetic ovariectomized (OD), and diabetic ovariectomized with eight weeks of genistein administration (ODG) and with eight weeks of swimming training (ODS) and with eight weeks of both of them (ODGS). High-fat nutrition and low dose streptozotocin injection were used for induction of diabetes. The effect of those treatments was evaluated by measuring lipid profiles, miRNA-133 gene expression, and Bcl-2, Bax, and IGF-1 protein expression levels. Inflammation and oxidative stress markers levels were also measured.Results: ovariectomy down-regulated cardiac miRNA-133, IGF-1, and Bcl-2 expression levels and increased MDA, OSI, TOS, TNF- α, and NF-κB levels plus a reduction in TAC. Diabetes induced an additive effect on the above-measured factors. Genistein improved oxidative and inflammation conditions and up-regulated miRNA-133, Bcl-2, and IGF-1 expression in OD rats. Genistein also enhanced the positive effect of exercise on miRNA-133, Bcl-2, and IGF-1expression in the heart, along with a reduction in Bax. The combined intervention was associated with improvement in oxidative and inflammation conditions. Histological observation showed some abnormality in cardiac tissue, which was improved by genistein or/and exercise treatment.Conclusion: genistein or/and exercise as a natural replacement therapy could improve diabetic-induced cardiac complications within the heart of ovariectomized rats.