This study aimed to investigate the association of serum hsCRP and urinary A1MG in patients with T2DM. Numerous investigations have proven that serum hypersensitive C-reactive protein (hsCRP) concentration in patients with type 2 diabetes mellitus (T2DM) is increased. Also, increased urinary alpha-1 microglobulin (A1MG) can be an early sign of renal damage, primarily on the proximal tubules in T2DM. Little information is available with respect to the associations of serum hsCRP levels and urinary A1MG in T2DM. A total of 520 patients with T2DM were recruited to participate in this study. Serum hsCRP and UA1MG (urinary alpha1-microglobulin to creatinine ratio), UACR (urinary microalbumin to creatinine ratio), UIGG (urinary immunoglobulin G to creatinine ratio), and UTRF (urinary transferrin to creatinine ratio) were obtained. The association of serum hsCRP level and each urinary protein parameter was analyzed by using the regression analysis, respectively. LnhsCRP was positively associated with the lnUA1MG in all three linear regression models (adjusted β in model 3=0.122, SE=0.027, P<0.001). Furthermore, the high hsCRP group (hsCRP > 3mg/L) was associated with increasing risk of high UA1MG (adjusted OR in model 3=1.610, 95% CI 1.037-2.499, P=0.034) by logistic regression. This study suggests that serum hsCRP levels independently associate with UA1MG in patients with T2DM. Further research is warranted to elucidate these interactions.