The objectives of this study were to evaluate the pharmacodynamics and pharmacokinetics of vanadyl acetylacetonate (VAC) in rats. Pharmacodynamic study was carried out using non-diabetic and diabetic rats by subcutaneous (s.c.) and intragastric (i.g.) administrations at single dose or multiple doses. Pharmacokinetic study was performed using non-diabetic rats. Results showed that VAC resulted in a significant decrease of plasma glucose levels in diabetic rats in all dosing levels, and nearly restored hyperglycemic values to normal values after s.c. injection at a single dose of 2, 4, and 8 mg vanadium (V)/kg, or after i.g. administration at multiple doses of 3 and 6 mg V/kg once daily for seven consecutive days, respectively. The VAC could be rapidly absorbed and T-max values ranged from 0.9 +/- 0.3 h for s.c. injection to 3.0 +/- 0.9 h for i.g. administration. The average absolute bioavailabilities for i.g. administrations at a single dose of 3, 6, and 10 mg V/kg were 34.7%, 28.1%, and 22.8%, respectively. After i.g. administration at a single dose of 10 mg V/kg, the average elimination half-lives obtained from non-diabetic rats were very long ranging from 144.7 +/- 8.7 h in plasma to 657.3 +/- 34.8 It in femur tissue. In conclusion, VAC widely distributed in various tissues and accumulated more in the femur tissue. The time to reach maximal vanadium level after s.c. injection or i.g. administration was not coincident with the time to reach maximal hypoglycemic effect. The accumulated vanadium in bone, kidney or other tissues may gradually release and exert a longer action. In present dosing levels and administration routes, VAC was effective for lowering plasma glucose levels in diabetic rats and could reverse the higher triglyceride and cholesterol levels to the normal ranges. VAC did not influence the insulin levels in plasma and not cause obvious toxic signs like diarrhea. (c) 2005 Elsevier Inc. All rights reserved.