As candidates for insulin mimetics, we prepared five vanadyl—dithiocarbamate complexes with VO(S4) coordination mode, and determined their structures by elemental analysis, visible absorption, IR and electron spin resonance spectra; the five complexes were bis(N,N-dimethyldithiocarbamate)oxovanadium(IV) (VO-DMD), bis(N,N-diethyldithiocarbamate)oxovanadium(IV) (VO-DED), bis(pyrrolidine-N-dithiocarbamate)oxovanadium(IV) (VO-PYD), bis(N-methyl,N′-d-glucamine-dithiocarbamate)oxovanadium(IV) (VO-MGD) and bis(sarcosine-N-dithiocarbamate)oxovanadium(IV) (VO-SAD). The insulin-mimetic activities were evaluated by in vitro and in vivo experiments. These complexes inhibited the release of free fatty acid (FFA) from isolated rat adipocytes, similar to the action of insulin. Among them, VO-PYD and VO-SAD complexes were found to be the most effective. In addition, the VO-PYD complex promoted the incorporation of glucose in rat L6 muscle cells. Based on these in vitro observations, both VO-PYD and VO-SAD complexes were given to streptozotocin-induced diabetic rats (STZ-rats) intraperitoneally or orally. Serum glucose levels of STZ-rats dropped from hyperglycemic levels to the normal range within 1 or 2 days after both intraperitoneal and oral administrations of the complexes. To understand the insulin-mimetic action of the VO-PYD complex, the organ distribution of vanadium was investigated. In normal rats treated with VO-PYD complex, vanadium was distributed in almost all tissues, indicating that the action of vanadium is not peripheral. In addition, vanadium was found in bone and kidney when VO-PYD was given. On the basis of these results, the VO-PYD complex is indicated to be a good agent to treat insulin-dependent diabetes in experimental animals.