BACKGROUND: Some Ficus species have been used in traditional African medicine in the treatment ofdiabetes. The antidiabetic potential of certain species has been confirmed in vivo but themechanism of activity remains uncertain. The aim of this study was to determine the activityand to investigate the mechanism of antidiabetic activity of ten selected Ficus species throughinhibition of a-amylase and a-glucosidase activity, and the possible relationship betweenthese activities, the total polyphenolic content and the antioxidant activity. METHODS: Dried acetone leaf extracts were reconstituted with appropriate solvents and used todetermine total polyphenolic content antioxidant activity, a-amylase and a-glucosidaseinhibitory activity. RESULTS: The crude acetone extract of F. lutea had the highest polyphenolic content (56.85 +/- 1.82 mgGAE/g of dry material) and the strongest antioxidant activity with a TEAC value of 4.80 +/- 0.90. The antioxidant activity of the acetone extracts of the Ficus species may not be ascribedto total polyphenolic content alone. The crude extract at a concentration of 0.5 mg/ml of F.lutea (64.3 +/- 3.6%) had the best a-glucosidase (sucrase) inhibitory activity. The EC50 of F.lutea (290 +/- 111 ug/ml) was not significantly different from that of F. sycomorus (217 +/- 69 ug/ml). The a-amylase inhibitory activity of F. lutea (95.4 +/- 1.2%) at a concentration of 1mg/ml was the highest among the Ficus species screened. The EC50 for F. lutea (9.42 +/- 2.01 ug/ml), though the highest, was not significantly different (p?0.05) from that of F.craterostoma and F. natalensis. It was apparent that the crude acetone extract of F. lutea is apartially un-competitive inhibitor of a-amylase and a-glucosidase. Based on correlationcoefficients polyphenolics may be responsible for a-glucosidase activity but probably not fora-amylase activity. CONCLUSION: Antidiabetic activity potential via inhibition of a-amylase and a-glucosidase was discoveredin Ficus lutea which has not been previously reported. The acetone extract of the leaves washigh in total polyphenolic content and antioxidant activity, and was a potent inhibitor of a-amylase activity. Research is underway to isolate the active compound(s) responsible for theantidiabetic activity and to confirm the in vitro antidiabetic activity and to investigate in vitrotoxicity.