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Clausena anisata (Wild) Hook (Family Rutaceae) is an indigenous Southern African medicinal plant used to treat diabetes mellitus and other diseases. Although, the blood glucose lowering effect of the methanolic C. anisata leaf extract has been confirmed in diabetic rats, the mechanism(s) remains unknown. This study investigated the effects of crude extracts of C. anisata leaves on selected enzymes associated with carbohydrate metabolism, in order to determine the mechanism of action related to hypoglycaemic effects of C. anisata. Crude C. anisata leaf extracts were investigated for their inhibitory effects against human urinary α-amylase, α-glucosidase and glucose 6-phosphatase in vitro as well as rat α-amylase and α-glucosidase in vivo. Aqueous and methanolic extracts strongly inhibited (>80%) α-amylase and moderately inhibited (60 and 58%, respectively) rabbit hepatic glucose-6phosphatase. These two extracts were less potent inhibitors of α-amylase than acarbose and significantly more potent inhibitors of G6Pase than sodium vanadate. Acetone and hexane extracts strongly inhibited (> 80%) Bacillus stearothermophillus α-glucosidase. Oral administration of acetone extract to fasted normal and streptozotocin-induced diabetic rats, 30 min before oral loading of both starch and maltose failed to prevent the rise in postprandial hyperglycemia in these animals. The in vitro inhibition of glucose-6-phosphatase by the aqueous and methanolic extracts of C. anisata needs to be confirmed in vivo. Results of this study suggest that the previously reported hypoglycemic activity of C. anisata extract could not be attributed to the inhibition of intestinal carbohydrate hydrolyzing enzymes.