Flavonoids are widely used for the treatment of chronic venous insufficiency (CVI). In clinical trials, micronized purified flavonoid fraction (MPFF, 450 mg diosmin plus 50 mg hesperidin, Daflon 500 mg) has demonstrated its activity in CVI by improving venous tone and vein elasticity assessed by plethysmography. Randomized, double-blind, placebo-controlled clinical studies have shown an improvement in signs and symptoms related to CVI and a decrease in leg circumferences at the levels of the ankle and calf. The effect of MPFF on microcirculatory parameters suspected of participating in the pathophysiological process of venous ulceration has been investigated in patients. These include hemorheological parameters and transcutaneous oxygen tension measurements, which were shown to improve after treatment with MPFF. Finally, a randomized double-blind, placebo-controlled clinical study has shown that MPFF treatment for 2 months, in addition to standard compression therapy, accelerates leg ulcer healing in patients with ulcers ≤10 cm.