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 (PPBcl-2 mRNA and Trx protein expression were significantly decreased (PBax mRNA, TXNIP and ASK1 protein expression were significantly increased (PPPPPBcl-2 mRNA and Trx protein expression were increased (PPBax mRNA, TXNIP and ASK1 protein expression were significantly decreased (PP