Background: Globally, highest hematologic malignancy in prevalence is considered chronic lymphocytic leukemia (CLL). The expression of angiopoietin-2 (Ang2) and tyrosine kinase with immunoglobulin and endothelial growth factor homology domains (Tie1), two critical components of the Ang-Tie2 pro-angiogenic pathway, in CLL cells has been demonstrated. Objective: Clarification of Tie2-expressing monocytes' (TEMs) involvement in the pathophysiology of CLL is the goal of this study. Patients and Methods: The study was case control, which was performed on 21 CLL patients; their age ranged from 46 to 71 with a mean of 58.2 ± 6.9, in addition to 21 age and sex matched healthy control subjects. Full medical histories, clinical examinations, and laboratory tests were conducted on all individuals. The percentage of TEMs in peripheral blood was determined by flow cytometry and their phenotypic characteristics defined as CD14+/CD16+/Tie-2+ cells. Results: Compared to the control group, there was a statistically significant increase in TEMs in the cases group. Among the cases group there was a statistical significant increase in LDH, uric acid, WBCs, reticulocyte, CD 38 β2 microglobulin and TEMS and statistical significant decrease in Hb with increase Binet stage. There was a statistical significant +ve correlation between TEMs and LDH, WBCs, reticulocytes, CD38 and β2 microglobulin. Also, there was a statistical significant negative correlation between TEMs and Hb and platelets count among the cases group. TEMs percentage had sensitivity, specificity and accuracy (100%) in diagnosis of leukemia at cut off > 20.95%. Conclusion: TEMs could be a part of CLL pathogenesis which can be a predictor of disease progression alongside with other prognostic indicators.