Abstract: AIM: To observe the effects of globular adiponectin (gANT) on endothelial dysfunction in hyperlipidemic rats and to investigate the mechanisms involved. METHODS: Male Sprague Dawley rats aged 8 weeks were randomly fed with a regular or high-fat diet for 14 weeks. Caval blood was drawn to measure the lipid profile and ANT levels. Aorta was isolated and incubated with gANT. The influences of gANT on the vasorelaxation response to acetylcholine (ACh), superoxide production and expression of p-eNOS and iNOS were determined. RESULTS: Compared with rats fed with a normal diet, animals fed a high-fat exhibited significantly increased cholesterol, triglyceride and ANT concentrations (P<0.01, P<0.05, P<0.05, respectively), endothelium dysfunction ［percentage of maximum vasorelaxation: (70.3±3.3)% vs.(95.2±2.5)%, P<0.01］, increased superoxide production (P<0.01) and reversed expression of nitric oxide synthase in vessel tissue. Treatment with gANT significantly improved the vasorelaxation response to ACh (P<0.01), attenuated overproduction of superoxide (P<0.01), increased eNOS phosphorylation (P<0.05) and reduced iNOS levels (P<0.01) in hyperlipidemic vascular segments. CONCLUSION: gANT improves endothelial dysfunction by enhancing bioactive NO production and preserving its bioactivity.