Many polyphenolic compounds are poorly digested, and have low bioavailability due to their long chain lengths and chemical composition. A processed, flavanol-rich lychee fruit extract (FRLFE) that is higher in flavanol monomers, dimer and trimers than its unprocessed counterpart, was tested in a variety of models. First, mature visceral adipocytes were treated with 0, 3, 10 or 30 microg/mL FRLFE (day 6-8). Compared with the controls, the treated cells had lower triglyceride concentrations, less lipid accumulation and a smaller lipid droplet size. Adiponectin release was significantly greater in cells receiving 3 or 10 microg/mL FRLFE than in the controls. Second, rats given a single dose of 50 or 100 mg/kg FRLFE had significant increases in plasma (-)-epicatechin, 3'-O-methyl-(-)-epicatechin, and (+)-catechin levels, peak values were at approximately 2 h and appreciable concentrations were still detected at 6 h. Rats supplemented daily for 1 week with 50 or 100 mg/kg FRLFE had significantly elevated metabolite concentrations. In response to an oxidative stress, erythrocyte membrane integrity was significantly improved in the 100 mg/kg FRLFE group. Third, 7-month-old mice fed a 200 mg/kg FRLFE diet for 10 months showed a significant decrease in glucose, triglyceride and lipid peroxide levels compared with mice fed a control diet. Collectively, these results support the concept that the flavanols present in FRLFE are well absorbed and bioactive.