To study the mechanisms of vascular dysfunction in diabetes mellitus, we examined the responses of the aorta to adrenomedullin (AM) and angiotensin II (Ang II) in obese Zucker (OZ) rats, lean Zucker (LZ) rats and OZ rats administered fluvastatin (OZ+flu). AM-induced endothelium-dependent vasorelaxation was impaired in OZ rats compared with LZ rats, and fluvastatin restored AM-induced endothelium-dependent vasorelaxation (%tension at 10^-7 mol/L AM, LZ -85.1±3.1%: OZ -50.7±2.5%: OZ+flu -75.6±2.7%). Expression of eNOS and Akt phosphorylation in response to AM (10^-7 mol/L) were also diminished in OZ rats. Fluvastatin restored the eNOS expression and Akt phosphorylation (eNOS expression (relative intensity), LZ 2.3± 0.4: OZ 1.0±0.2: OZ+flu 1.8±0.3; Akt phosphorylation (relative intensity), LZ 2.3± 0.2: OZ 1.0±0.3: OZ+flu 1.9±0.2). Ang II-induced vasoconstriction was enhanced in the aortic rings of OZ rats compared to LZ rats and this enhanced vasoconstriction was partially normalized by fluvastatin, and was abolished when the aorta of OZ rats was preincubated with the Rho kinase inhibitor Y-27632. GTPS-induced contraction of permeabilized aortic smooth muscle cells, which is an indicator of the Rhodependent Ca²⁺ sensitization of contraction, was enhanced in OZ rats compared with LZ rats, and this enhanced contraction was suppressed in OZ+flu rats. These results suggested that endothelium-dependent vasorelaxation was impaired and Ca²⁺ sensitization of contraction was augmented in blood vessels of OZ rats and that fluvastatin restored vascular function by activating the Akt-dependent pathway and inhibiting the Rho-dependent pathway.