This study was undertaken to investigate the preventive mechanism of Amomum xanthoides extract against the development of alloxan-induced diabetics of mice. Pretreatment of mice with A. xanthoides extract via intraperitoneum prevented alloxan-induced hyperglycemia and hypoinsulinemia in a dose dependent manner. Histological examination of pancreatic tissue from A. xanthoides extract treated mice showed that the islet cells remain unaffected by alloxan treatment. NFkappaB activation in the pancreas 30 min after alloxan injection (60 mg/kg, iv), as assessed by an electrophoretic mobility shift assay, was not detected in the mice pretreated with A. xanthoides extract. These results suggest that NFkappaB activation may be one of the critical determinant in the progression of the disease. Considering the preventive effect of A. xanthoides extract from alloxan-induced diabetics development, these results may provide the possible therapeutic value of A. xanthoides extract for the prevention of diabetes mellitus progression.