Background <p>Diabetic heart disease is marked by structural, functional, and molecular alterations in the myocardium. We investigated the effects of exercise training on oxidative phosphorylation-related genes in the diabetic heart.</p> Methods <p>Male mice C57BL/6JNarl (<i>n</i> = 24) were randomly divided into three equal groups: STZ-induced diabetic group with 12-week exercise training (DM-EX); diabetic group (DM); a non-diabetic control group. After completion of exercise training, samples from the soleus and heart tissues were collected from all the mice. Out of eight mouse samples from the DM and DM-EX, two left ventricles from either group were randomly selected and processed for RNA extraction and microarray analysis.</p> Results <p>Exercise training changed the expression of 517 genes (<i>P</i> &lt; 0.05); 380 upregulated,137 downregulated. Enrichment analysis depicted that apoptosis, diabetic cardiomyopathy, and oxidative phosphorylation were most significantly regulated. Pathway analysis revealed that exercise training upregulated 17 key oxidative phosphorylation genes, including complex I (Ndufa13, Ndufb4, Ndufb8, Ndufb9, Ndufc1, Ndufc2, Ndufs4, Ndufv2), complex III (Uqcrfs1, Uqcrh), complex IV (Cox5A, Cox7A, Cox17), and complex V (Atp5e, Atp5g3, Atp5k, Atp5l).</p> Conclusion <p>Exercise training amplifies the gene expression concerned with oxidative phosphorylation in the diabetic heart, showing its potential to modulate molecular pathways that influence cardiac functions and improve the diabetic heart.</p> Clinical trial number <p>Not applicable.</p>