We prepared and characterized [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadate(IV)(4À), [VO(tpps)], and its in vitro insulin-mimetic activity, metallokinetic features in the blood of healthy rats, and in vivo hypoglycemic effect in streptozotocin (STZ)-induced diabetic mice (STZ mice) were investigated. The results were compared with those of previously proposed insulin-mimetic [meso-tetrakis(1-methylpyridinium-4-yl)porphyrinato]oxovanadium(IV)(4+), [VO(tmpyp)], and vanadium(IV) oxide sulfate. The in vitro insulin-mimetic activity, the retention time and bioavailability of [VO(tpps)] in blood were considerably better than those of [VO(tmpyp)] and vanadium(IV) oxide sulfate. [VO(tpps)] caused a significant hypoglycemic effect in STZ mice within 8 h following a single oral administration of the complex at 15 mg V/kg of body mass without ascorbate; this effect was sustained for at least 60 h. [VO(tpps)] normalized the hyperglycemia of STZ mice within 2 days when administered orally at 4-10 mg V/kg of body mass for 18 days. Vanadium, as determined by instrumental neutron activation analysis, was distributed in the tissues examined in the following decreasing order: bones, kidneys, liver, lungs, spleen, heart, pancreas, muscles, fatty pads, and brain. The improvement in diabetes was supported by oral glucose tolerance test, HbA 1c level and blood pressure. Based on the above results, [VO(tpps)] is an orally active oxovanadium(IV)-porphyrin complex for treating type 1 diabetic animals.