Abstract: Objective To investigate the effects of genistein (Gen) on myocardial injury in diabetic rats and explore its mechanisms. Methods Male SD rats were randomly divided into normal (N) group, diabetic (D) group, Gen 5 mg/kg treatment (L) group and Gen 25 mg/kg treatment (H) group (n=8 for each group). Intraperitoneal injection of streptozotocin was utilized to establish type 1 diabetic rat model. After successful building models, from the fifth week, the rats in the L and H groups were daily gavaged with 5 mg/kg and 25 mg/kg Gen solution, respectively. After 4 weeks of treatment with Gen, the hemodynamic parameters and fasting blood glucose (FBG) level were measured. The morphological structure and ultrastructure of myocardium were observed using HE staining and transmission electron microscopy, respectively. The levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), malondialdehyde (MDA), glutathione (GSH) and Caspase-3 in myocardial tissue were measured. The levels of myocardial Bcl-2 and Bax at mRNA expression were detected using RT-PCR. The levels of myocardial thioredoxin (Trx), Trx-interacting protein (TXNIP) and apoptosis signal regulating kinase 1 (ASK1) at protein expression were detected using Western blot. Results Compared with the N group, the FBG, TNF-α, IL-1β, IL-6, MDA and Caspase-3 levels were increased (P<0.01), while hemodynamic parameters and GSH content were decreased (P<0.01), the myocardial morphological structure and ultrastructure were damaged in the D group. The levels of Bcl-2 mRNA and Trx protein expression were significantly decreased (P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly increased (P<0.01) in the D group. Compared with the D group, in the L and H groups, there was no significant difference in FBG, the TNF-α, IL-1β, IL-6, MDA and Caspase-3 levels were decreased (P<0.05, P<0.01), while the hemodynamic parameters and GSH content were increased (P<0.05, P<0.01); the myocardial morphological structural and ultrastructural damages were alleviated; the levels of Bcl-2 mRNA and Trx protein expression were increased (P<0.05, P<0.01), while the levels of Bax mRNA, TXNIP and ASK1 protein expression were significantly decreased (P<0.05, P<0.01). Conclusion Gen exhibits a protective effect on myocardial injury in diabetic rats, and the mechanisms may be associated with the reduction of inflammatory reaction, the regulation of Trx system expression, and the inhibition of oxidative stress and cell apoptosis.