In the more advanced stages of chronic venous insufficiency, stasis in the skin microcirculation is associated with a decreased red blood cell velocity and an increase in packed cell volume related to the red blood cell piling phenomenon. Although the main factor determining blood viscosity is packed cell volume, the direct relationship between this variable, viscosity and velocity is no longer valid at the microcirculatory level (sigma effect). Viscosity is influenced by blood composition and red blood cell deformability. The aim of this open pilot study was to verify the variations in capillary packed cell volume in comparison with the velocity in 24 patients with third-stage chronic venous insufficiency before (day 1) and after (day 28) a 28-day treatment with Daflon 500 mg, a micronized purified flavonoid fraction consisting of diosmin, 450 mg, and hesperidin, 50 mg, per tablet, 1 g/day, and then 14 days (day 42) after cessation of treatment. Ankle skin microcirculation was evaluated by dynamic capillaroscopy. Values of relative capillary packed cell volume were calculated by a densitometric method, and red blood cell velocity was calculated using the cross-correlation simplified method. Relative capillary packed cell volume (mean +/- SD) significantly (p = 0.001) increased from day 1 (64.10 +/- 9.34%) to day 28 (72.89 +/- 5.74%) and then decreased until day 42 (66.84 +/- 7.48%). In the same patients, red blood cell velocity (mean +/- SD) significantly (p = 0.041) increased from day 1 (0.26 +/- 0.14 mm/sec) to day 28 (0.35 +/- 0.11 mm/sec) and then remained stable until day 42 (0.33 +/- 0.16 mm/sec). Two possible explanations can account for this apparent discrepancy: first, dissociation between viscosity and velocity due to the Fahraeus-Lindqvist effect (sigma effect); and secondly, increased deformability of red blood cells leading to an increased red blood cell velocity despite an increased packed cell volume. It can be concluded that Daflon 500 mg seems to have a beneficial haemorheological effect, resolving the stasis with an increase in red blood cell velocity. A concomitant increase in relative packed cell volume and red blood cell velocity after therapy suggests an improvement of the flexibility of red blood cells.