BACKGROUND: High prevalence of anemia in diabetes mellitus (DM) determines the relevance of studying its pathogenetic aspects, the role of anemia in DM complications development and the issue of differential diagnosis between iron deficiency anemia (IDA) and anemia of chronic disease (ACD)).AIM: To establish the diagnostic value of classical parameters for diagnosing anemia in DM and propose an optimized algorithm for the differential diagnosis of ACD and IDA in DM type 1 and 2 using new markers.MATERIALS AND METHODS: The observational, single-centre, comparative, controlled, single-stage study. Patients underwent assessment of glycated hemoglobin, creatinine, microalbuminuria; indicators of iron metabolism — hematocrit, the number of erythrocytes, reticulocytes, hemoglobin, serum iron, transferrin, ferritin, the level of soluble transferrin receptors (sTfR), sTfR/logFerpitin index, and inflammation markers — erythrocyte sedimentation rate (ESR), leukocyte count, high sensitive CRP and TNF-α. ROC-analysis was used to assess the differential diagnosis markers informative content.RESULTS: We examined 135 patients: 51 with DM 1 and 84 with DM 2. The patients were stratified into groups based on anemia type: 1) ACD 2) IDA 3) latent iron deficiency 4) without ferrokinetics disorders. According to the ROC-analysis in DM patients, the following parameters had high information content in ACD. ESR — sensitivity 92%, specificity 85%, diagnostic threshold 26.5 mm/h (area under the curve (AUC) 0.943; p<0.0001); leukocyte count — sensitivity 69%, specificity 64%, diagnostic threshold 7.50x109/l (AUC 0.727; p=0.007), microalbuminuria — sensitivity 71%, specificity 72%, diagnostic threshold 29.5 mg/l (AUC 0.744; p=0.003). In DM sTfR and the sTfR /logFerritin index had high information content in IDA at diagnostic thresholds different from those for general population. The sensitivity of sTfR 71%, the specificity 71%, diagnostic threshold 1.42 ng/mL (2.9 ng/mL for general population) (AUC 0.765; p=0.024). The sensitivity of sTfR/logFerritin index 100%, the specificity 97%, diagnostic threshold 1.48 (2.0 for general population) (AUC 0.983; p=0.024).CONCLUSION: In differential diagnosis of IDA and ACD in DM, ESR, leukocyte count, microalbuminuria, sTfR and sTfR/logFerritin index have a high diagnostic value. This allows proposing them as additional markers for differential diagnosis of anemia in DM.