To treat both insulin-dependent type 1 and non-insulin-dependent type 2 diabetic mellitus, two potent antidiabetic vanadyl pyridone complexes, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), (VO(opt)2), and bis(1-oxy-2-pyridonato)oxovanadium(IV), (VO(opd)2), were proposed on the basis of the results of diabetic model animals by using a concept of equivalent transformation, which has been proved to be effective in changing the chemical property of a compound. Their physico-chemical properties, chemical specications, in vitro insulin-mimetic activity in isolated rat adipocytes, in vivo antidiabetic activity in both type 1 and type 2 diabetic animals, and metallokinetic feature of the vanadyl species in the blood flow of alive rats by using blood circulation monitoring-electron paramagnetic resonance (BCM-EPR) were examined. Both complexes exhibited higher in vitro insulin-mimetic activity than VOSO4, and the activity of VO(opt)2 was superior to that of VO(opd)2. However, on oral administration to type 1 diabetic rats, VO(opd)2 was more effective at lower dose than VO(opt)2. The results are supported by chemical specifications and metallokinetic (kinetic of metal disposition) parameters.