OBJECTIVE: To describe relationships of retinal vascular calibre with plasminogen activator inhibitor-1 (PAI-1) and other cardiovascular risk factors in people with type 2 diabetes. METHODS: We recruited 112 community-based persons aged 44-83years with type 2 diabetes, photo-documented retinal status using a digital fundus camera, and measured traditional and novel vascular risk factors. Retinal arteriolar and venular calibre and the arterio-venous ratio (AVR) were determined from fundus photographs using a validated computer-assisted method. RESULTS: In adjusted linear regression models, PAI-1 activity was strongly associated with all measures of retinal vascular calibre: positively with arterioles (p=0.005) and AVR (p=0.001), and inversely with venules (p=0.001). In addition, wider arterioles were independently associated with waist-hip ratio (p<0.0001), HDL-C (p=0.015), and lower systolic blood pressure (p=0.042), whereas narrower venules were associated with older age and a higher albumin excretion rate. Neither arteriolar nor venular calibre was associated with plasma total homocysteine or C-reactive protein concentration. CONCLUSION: Retinal vascular calibre is independently associated with PAI-1 activity in type 2 diabetes. This finding supports a role for PAI-1 activity in the microvasculature of persons with type 2 diabetes and may explain the link between retinal vascular calibre and cardiovascular disease.