Objective:To explore the protective effect of the drug Semecarpus anacardium(S.anacardium) on altered glucose metabolism in diabetic rats.Methods:Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ)(35 mg/kg b.w.).Seven days after STZ induction,diabetic rats received nut milk extract of S.anacardium Linn.nut milk extract orally at a dosage of 200 mg/kg daily for 4 weeks.The effect of nut milk extract of S.anacardium on blood glucose,plasma insulin,glucose metabolising enzymes and GSK were studied.Results:Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA-βand decrease in HOMA -IR.The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes.The drug also effectively ameliorated the alterations in GSK-3 mRNA expression.Conclusions:Overall,the present study demonstrates the possible mechanism of glucose regulation of S.anacardium suggestive of its therapeutic potential for the management of diabetes mellitus. Objective: To explore the protective effect of the drug Semecarpus anacardium (S. anacardium) on altered glucose metabolism in diabetic rats. Methods: Type 2 diabetes mellitus was induced by feeding rats with high fat diet followed by single intraperitoneal injection of streptozotocin (STZ) (35 mg / kg bw). Seven days after STZ induction, diabetic rats received nut milk extract of S. anacardium Linn. Nut milk extract orally at a dosage of 200 mg / kg daily for 4 weeks.The effect of nut milk extract of S.anacardium on blood glucose, plasma insulin, glucose metabolising enzymes and GSK were studied. Results: Treatment with SA extract showed a significant reduction in blood glucose levels and increase in plasma insulin levels and also increase in HOMA-β and decrease in HOMA-IR The drug significantly increased the activity of glycolytic enzymes and glucose-6-phosphate dehydrogenase activity and increased the glycogen content in liver of diabetic rats while reducing the activities of gluconeogenic enzymes The drug also effectively ameliorated the alterations in GSK-3 mRNA expression. Overall: the present study demonstrates the possible mechanism of glucose regulation of S. anacardium suggestive of its therapeutic potential for the management of diabetes mellitus.