OBJECTIVE To evaluate if the micronized purified flavonoid fraction (MPFF) treatment could reduce the side effects of sclerotherapy (a procedure frequently used to treat venous disease manifestations) by minimizing the inflammatory response within the surrounding tissues. METHODS Twenty-two male New Zealand rabbits were treated by gavage with micronized purified flavonoid fraction (MPFF; 300 mg/kg/day) or vehicle (10% lactose solution) during 21 consecutive days, starting 7 days before sclerotherapy. The sclerotherapy consisted of an injection containing 5% ethanolamine oleate solution in the rabbit's dorsal ear vein. Before and after sclerotherapy, venular and arteriolar diameters, microvascular permeability, functional capillary density (FCD), number of rolling and sticking leukocytes were evaluated on ear microcirculation. Images of the sclerotherapy site were taken before and after the procedure. RESULTS Compared to placebo, MPFF treatment prevented the increase in venular diameter, preserved FCD (P < 0.001) and reduced the number of leaky sites (P < 0.001) and sticking leukocytes (P < 0.001). Imaging confirmed these effects on thrombosis and perivascular edema of the sclerosed vein, 14 days after procedure. CONCLUSIONS MPFF treatment limited the postsclerotherapy inflammation in surrounding microvascular network, suggesting that MPFF may prevent undesirable secondary effects of the procedure in this animal model. This study warrants further investigation for its use in clinical conditions.