OBJECTIVE: To study the effect of different phenolic compounds and red wine on pulmonary metastatic melanoma. METHODS: Swiss mice were inoculated with 500000 melanocytes B16F10 and given oral doses of diosmin, grape seed extract (GSE) and red wine. A macroscopic count was made of the metastatic nodules on the lung surface and a microscopic study by image analysis of five sections, calculating the implantation percentage and tumoral growth and invasion indices. RESULTS: Macroscopically, the group treated with diosmin showed the greatest reduction (52%) in the number of metastatic nodules compared with the control group, which was treated with ethanol, while GSE and red wine caused decreases of 26.07 and 28.81%, respectively. Microscopically, there was a decrease in the implantation percentage after the administration of diosmin (79.4%) and red wine (20.19%), and an increase of 2.12% after the administration of GSE, all relative to the ethanol-treated control. As regards the growth index, diosmin produced a reduction of 67.44% and red wine a reduction of 20.62%, while GSE again produced an increase (25.33%). The reductions in the invasion index were 45.23, 31.65 and 17.57% with diosmin, GSE and red wine, respectively. CONCLUSIONS: Diosmin originated the greatest reduction in pulmonary metastases, both at the macroscopic and microscopic levels.