This study was designed to evaluate the effect and toxicity of administration of vanadium (IV, V) absorbed by Coprinus comatus (VACC) on alloxan-induced and sucrosefed hyperglycemic mice, respectively. The blood glucose, lipid profile, and the organ masses of the mice were analyzed. After the mice were administered with VACC, the blood glucose and the lipid profile of hyperglycemic mice decreased, irrespective of the VACC produced by vanadium (IV) or vanadium (V). However, the organ masses of the mice were significantly different after the mice were treated with vanadium (IV) and vanadium (V) 9 weeks later. The results indicate both vanadium (IV) and vanadium (V) absorbed in C. comatus have hypoglycemic activity on hyperglycemic mice. However, vanadium (IV) absorbed in C. comatus is less toxic to mice than vanadium (V).