Objective of the study. The comparative analysis of mitogenic factors in the venous wall of the systemic and regional circulation of the lower extremities. Material and methods. The study involved 34 patients presenting with clinical class C2—C3 (n=28) and class C4 (n=6) venous insufficiency in whom the endothelial markers were detected including vascular endothelial growth factor (VEGF-A), fibroblast growth factor (FGF basic), and endothelin-1.  The blood samples were taken from systemic (cubital vein) and  regional (great saphenous vein) circulation in 32 and 21 cases respectively. The results were compared with the respective values obtained in the analysis of the blood samples from systemic circulation of 11 healthy volunteers. In 9 patients presenting mostly with the clinical class C2—C3 venous disease, dynamics of endothelial peptides was studied before and after intake of the red grape leaf extract (720 mg daily) during 2 weeks. Results. The patients presenting with varicose veins suffered endothelial dysfunction characterized by the enhanced plasma levels of fibroblast growth factor and vascular endothelial growth factor up to (6.3±0.4 pg/ml; p<0.01) and (134.2±6.6 pg/ml; p<0.05) respectively compared with the healthy subjects. In the period of varicose vein development, the hyperproduction of endothelial growth factor by vascular endothelium in the great saphenous vein (up to 169.3±10.2 pg/ml; p<0,2) in comparison with that in systemic circulation was documented. This finding was attributed to the impaired adaptation to regional orthostatic phlebohypertension and tissue hypoxia that resulted in the adaptive remodeling of the venous wall. Phlebotropic therapy increased the plasma level of the venoconstrictor endothelin-1 by a factor of 3 (up to  0.6±0.1 pg/ml; p<0.02) and decreased manifestations of venous insufficiency. Conclusion. The present study has demonstrated an increase in the plasma levels of the vascular endothelial growth factor and  the fibroblast growth factor in the patients with primary varicose veins suggesting endothelial dysfunction. It is concluded that the hyperproduction of mitogenic peptides by venous endothelium associated with primary varicose veins may cause compensatory remodeling of the venous wall.