Together, our results showed that inhibition of Sirt6 expression induced by sh-Sirt6 in the kidneys of db/db and db/+ mice could promote the EMT, aggravate the pathological characteristics of DN, and exacerbate the tubular injury, suggesting that Sirt6 has a protective role in the kidney injury induced by DN. The gene discussed is SIRT6; the disease is liver dysplastic nodule.