Abstract: This study was aimed to evaluate the antidiabetic effect of sea cucumber saponin on the spontaneous diabetes mice. Inhibition of the sea cucumber saponin on alpha glycosidase, alpha amylase, which were related with the glucose metabolism enzymes were observed in vitro experiment. Male C57BL/KsJ (db/db) and C57BL/KsJ were equally divided into three groups, normal group (C57BL/KsJ) , model group (C57BL/KsJ (db/db) and sea cucumber saponin group (C57BL/KsJ (db/db) . Mice in Saponin groups feed add 0.07% sea cucumber saponin feed for five weeks. Fasting plasma glucose level, fasting insulin level and glucose tolerance of all groups were determinded. Sea cucumber saponin could obviously inhibits alpha glycosidase activity, certain inhibition to alpha amylase also. Sea cucumber saponin group could reduce the fasting blood glucose (p<0.01) , serum insulin (p<0.05) and improve the glucose tolerance abnormal (p <0.05) of spontaneous diabetes mice. The results suggested that sea cucumber saponin had good effect on controlling blood glucose level and improving insulin resistance of spontaneous diabetes mice, its hypoglycemic mechanism might be related to the inhibition on glucose metabolism enzymes.