In the present study, we found that a complete loss of Smad3 in db/db mice was required to prevent the development of DCM as Smad3 haploinsufficiency (Smad3+/− db/db) mice, like Smad3 WT‐db/db mice, showed no protective effect on cardiac dysfunction and progressive myocardial inflammation and fibrosis. The gene discussed is SMAD3; the disease is inflammation.