The present study shows for the first time that the leaf extract of Cissampelos pareira (CLE) has potential anti-hyperglyaemic activity in fructose-induced and fructose-aloxan-induced diabetic rats as judged from the significant reduction in serum glucose and percent glycosylated haemoglobin. The significantly higher percent ?-cell granulation scores in the CLE-treated animals give further support to these findings. The reduction in the level of triglyceride and cholesterol indicates its beneficial effect on carbohydrate and fat metabolism. The most characteristic feature of the ?-cells failure is a specific defect in glucose sensing characterized by loss of first phase insulin secretion in response to a glucose stimulus. In this experiment, the fructose-fed rats exhibited impaired glucose tolerance in the oral glucose tolerance test indicating ?-cells failure. The improvement in the glucose tolerance in the CLE-treated rats shows its important role in the preservation of islet ?-cells function.Significant enhancement of the macrophage phagocytosis in the CLE-treated hyperglycaemic rats indicates its possible role in immuno-modulation.