Since insulin-dependent diabetes mellitus (IDDM), which causes many severe secondary complications, is characterized by hyperglyceria due to absolute deficiency of insulin, the diseases is controlled by daily injection of insulin. Therefore, the development of insulin replacements of mimetics upon oral administration is an important investigation. Recent studies indicate that vanadium, which is proposed to be one of essential trace elements in animals and humans, relates to both glucose and lipid metabolisms, and the metal in turn shows insulin-mimetic effect. Thus several types of vanadium complex have been proposed to be insulin mimetics. In 1990, we proposed first vanadyl-cysteinate complex, which normalized the blood glucose level of IDDM rats on oral administration. On the other hand, simple vanadium compounds such as vanadyl sulfate and sodium vanadate have been reported to be useful to treat human non-insulin-dependent diabetes mellitus (NIDDM). Based on the observations, we have developed several types of vanadyl complexes with different coordination modes such as VO(0 4 ), VO(N 4 ), VO(S 4 ), VO(O 2 N 2 ), VO(S 2 N 2 ) and VO(O 2 S 2 ), and found that vanadyl-methylpicolinate complex with long acting character and low toxicity is the most effective to treat IDDM as well as NIDDM rats, when administered orally. The mechanism was also studied with respect to the pharmacokinetic analysis and vanadium distribution in animals. J. Trace Elem. Exp. Med. 12:393-401, 1999.