Critical shear stress (CSS, mPa) is an index of red blood cell (RBC) aggregability, defined as the minimal shear stress required to disperse RBC aggregates. This study aimed to investigate the association between CSS and the risk of diabetic kidney disease (DKD). A total of 421 (mean age, 58.1 ± 11.5 years; male, 250) individuals with T2DM were enrolled and divided into three groups according to CSS level. CSS was measured using a transient microfluidic technique. DKD was defined as a glomerular filtration rate (GFR) <60 ml/min/1.73 m2 or a urine albumin-to-creatinine ratio (uACR) ≥30 mg/g. CSS was significantly higher in patients with DKD than in those without (317.43 ± 125.11 vs 385.22 ± 182.89, p < 0.001). Compared to the lowest CSS tertile, the highest CSS tertile was independently associated with the risk of DKD after adjusting for age, sex, duration of diabetes, presence of hypertension and haemoglobin. The cut-off value of CSS for DKD was approximately 310 mPa. These results suggest that haemorheologic changes may contribute to DKD, and further prospective studies are warranted to determine the role of CSS as a DKD screening tool.