This study found, for the first time, that the serum and urine levels of HMGB1 in patients with DKD were significantly higher than those in the non-DKD diabetic and healthy control populations (2.5–10 times), and with the aggravation of DKD, serum HMGB1 levels increased significantly and was positively correlated with the serum TNFR-1 level. Here, HMGB1 is linked to diabetic kidney disease.