People of Asir region of Saudi Arabia chew Caralluma sinaica (CS) to lower glucose level. To establish its utility in diabetes mellitus we have under taken this study. The effect of CS on streptozotocin (STZ)-induced diabetic model as well as effect on oral glucose tolerance test were studied. The extract was shown to have positive test for possessing following chemical constituents like phenolic alkaloids, glycosides, flavonoids, coumarins, steroids and tannins. Administration of CS in different doses (50, 100, 150 and 200mg/kg, p.o.) to normal animals caused significant (P<0.01) decrease in glucose level. Prior administration of either CS (100mg/kg, p.o.) or glibenclamide (GB) (5mg/kg, p.o.) blocked the rise of glucose caused by the streptozotocin. Antidiabetic activity of CS was compared with clinically available drug GB. Administration of CS (100mg/kg, p.o.) to diabetic rabbits for 30 days has been shown to decrease plasma glucose level to almost normal level (P<0.001). Liver and kidney weight expressed as percentage of body weight significantly (P<0.05; P<0.01) increased in diabetic rabbits versus normal control (CNT). CS significantly (P<0.05) reversed the increasing weight of liver caused by STZ but not GB. STZ induced lowering of glycogen content of liver and muscle was reversed by both CS and GB. STZ induced a significant (P<0.001) increase in renal glycogen content this was almost normalized by CS (P<0.001) whereas GB significantly decreased (P<0.002) glycogen content. In oral glucose tolerance test administration of glucose increased plasma glucose level significantly in the diabetic control over the 2-h period. Compared to diabetic control plasma glucose levels in rabbits given CS or GB were significantly lower at all the time points that blood was sampled after oral glucose load. Comparing with the GB treatment blood glucose lowering effect was more pronounced for diabetic rabbits given CS. All these effects could explain the basis for use of this plant extract to manage diabetes mellitus.