Background: Early diagnosis of stroke, its treatment and rehabilitation are considered priorities in the state health care policy. Pharmacological intervention is used as a strategy to protect the neurons from the ischemic penumbra. Aim: To evaluate changes of functional state and levels of endothelial progenitor cells (EPC) in the circulation in ischemic stroke patients under administration of citicoline. Materials and methods: We assessed 11 patients in their early rehabilitation period of ischemic stroke (9 men and 2 women, mean age 58.4 ± 9.2 years). Patients from group 1 (n = 7) were given citicoline at dose 2000 mg/daily for 14 days, whereas patients from group 2 (n = 4) received regular treatment. Two healthy volunteers served as a control group. Circulatory EPC phenotype was assessed by multicolor laser flow cytometry and monoclonal antibody assay. Stroke severity and functional abilities were measured with NIHSS, Rankin scale and Rivermead mobility index. Results: Patients with ischemic stroke had decreased levels of early EPC, compared to healthy subjects. After 7 days of treatment in the group 1, there was a significant increase of circulatory EPC expressing VEGFR2+ up to 25.5 ± 20.9%, as well as an increase of early EPC numbers (CD117+ / CD133+) up to 18.8 ± 14.6%, compared to their respective baseline levels (21.9 ± 19.2 and 9.4 ± 5.4%) and compared to respective parameters in the group 2 (8.1 ± 2.7 and 5.5 ± 3.4%). In the group 1, severity of stroke and functional ability at baseline and at day 7 were as follows: NIHSS scores, 5.8 ± 4.9 and 3.5 ± 0.7, Rankin scale scores, 2.7 ± 1.3 and 2.3 ± 0.5, Rivermead mobility index, 8.8 ± 4.9 and 9.4 ± 4.8, respectively. In the group 2 corresponding parameters scored as 4.5 ± 2.3 and 3.3 ± 0.5, 2.5 ± 0.6 and 2.5 ± 0.4, 12.5 ± 1.3 and 12.7 ± 0.7, respectively. Conclusion: Treatment with citicoline in acute ischemic stroke promoted almost a 2-fold increase in early EPC levels. A decrease in neurologic deficiency and an improvement of functional status of patients with ischemic stroke were observed.