Objective To observe the correlation between serum miRNA-21 and diabetic nephropathy（DN） in different stages of TCM syndromes and laboratory indexes. Methods Sixty patients with type 2 diabetes mellitus（type 2 diabetes mellitusus， T2DM） and DN were divided into 4 groups， 15 in each group， and 15 healthy people in control group. Collect the data of four diagnoses in each group， and carry out TCM syndrome differentiation and typing. Serum miRNA-21 expression and serum creatinine（Scr）， urea nitrogen（BUN）， cystatin C（CysC）， serum albumin（Alb）， cholesterol（CHOL）， triglyceride（TG）， glomerular filtration rate estimated value（eGFR）， urinary protein quantification and blood rheology were checked in each group. Results The level of serum miRNA-21 in DN V stage、DNⅣstage、DNⅢstage was significantly higher than that in normal group（P<0.05）； DNⅣstage was higher than DNⅢstage（P<0.05）； There was no significant difference between T2DM group and normal group（P>0.05）， The level of serum miRNA-21 in DN V stage was significantly lower than that in DN Ⅳ stage（P<0.05）. In TCM syndrome differentiation， the proportion of yin deficiency and heat dryness syndrome was the lowest， qi and yin deficiency syndrome was the second（P<0.05）， spleen and kidney qi deficiency syndrome and yin and yang deficiency syndrome was the highest（P<0.05）， and there was no significant difference between spleen and kidney qi deficiency syndrome and yin and yang deficiency syndrome（P>0.05）. The expression of serum miRNA-21 was significantly increased in the deficiency of Qi and Yin， deficiency of spleen and Kidney Qi and deficiency of Yin and Yang（P<0.05）， especially in the deficiency of spleen and Kidney Qi and Yin and Yang groups（P<0.05）， but there was no significant difference between the deficiency of spleen and Kidney Qi group and that of Yin and Yang deficiency group（P>0.05）. There were 16 cases of dampness syndrome（26.7%）， 15 cases of phlegm syndrome（25%）， 29 cases of blood stasis syndrome（48.3%）. The proportion of blood stasis syndrome was the highest（P<0.05）， the serum miRNA-21 of blood stasis syndrome group was the highest（P<0.05）； There was no significant difference between dampness syndrome group and phlegm syndrome group （P>0.05）. The results of correlation study showed that the expression of serum miRNA-21 was positively correlated with BUN、Cr、Cysc and K value of erythrocyte sedimentation rate in patients with DN Ⅲ and DN Ⅳ， and negatively correlated with eGFR； while serum miRNA-21 was only positively correlated with K value of erythrocyte sedimentation rate in DN Ⅴstage. Conclusion The expression of serum miRNA-21 was significantly different in different stages of DN， and there might be some correlation between serum miRNA-21 and some laboratory indexes of DN patients.