The aim of this study: The aim of the study was to determine the percentages of monocyte subpopulations in patients with Crohn's disease treated with biological or non-biological therapy. Methods: Blood samples, taken from all research participants in the morning period after at least a 10- hour fast, were used for biochemical analysis and flow cytometry. Blood was taken from the antecubital vein using a polyethylene catheter. 100 microliters of whole blood were treated with Fc receptor blocking reagent (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany) to prevent nonspecific binding. In addition, 4 μL of anti-human CD14s PerCP-Cy5.5-conjugated antibodies (eBioscience, USA), 4 μL of phycoerythrin-conjugated antibodies reactive to human CD16 (eBioscience, USA), and 10 μL of mouse antibodies reactive to human CD44 conjugated with FITC (BD Pharmingen, San Diego, CA). The samples were incubated for 20 minutes at 25 °C in the dark. After lysing erythrocytes with additional lysis solution (Miltenyi Biotec GmbH, Bergisch Gladbach, Germany), monocytes were analyzed with a flow cytometer (BD Accuri C6, BD Biosciences, Belgium). Results: The results we obtained showed a twice higher percentage of CD14⁺⁺CD16⁺ monocytes in moderately active Crohn's disease compared to mild and severe (p = 0.002). Likewise, the use of non-biological therapy decreased by 2.3 times the percentage of non-classical CD14⁺CD16⁺⁺ monocytes, while patients who received biological therapy had a similar percentage as the control group. Conclusion: Biological therapy is more favorable than non-biological therapy because it does not lower the percentage of non-classical anti-inflammatory CD14⁺CD16⁺⁺ monocytes.