The prevalence of diabetes mellitus (DM) is increasing worldwide reaching epidemic proportions. The aim of the present study was to estimate the prevalence of DM in Thessaly, a large region of Central Greece, and to extrapolate our results to the population of the entire country. A random sample of 805 adults (421 females and 384 men) living in Thessaly, aged 18-80 years, was surveyed. After completing a questionnaire about health status and a thorough physical examination, a blood sample was obtained from each participant for biochemical analysis. Participants with fasting glucose levels between 100-125 mg/dl underwent an oral glucose tolerance test (OGTT). A second survey was also conducted, via telephone call-interviews, in a randomly selected sample age- and sex-stratified to the country's adult population in order to extrapolate the DM data from Thessaly to the whole country. The frequency of DM based on patient history and fasting blood glucose levels was 6.96%, comparable to that observed in the telephone-based nationwide survey (7.38%, p=0.669). However, after the OGTT an additional 3.72% of the population had undiagnosed DM, increasing DM prevalence to 10.68% (age adjusted 11.77%). The prevalence of pre-diabetes was 8.70%, with impaired fasting glucose at 5.84% and impaired glucose tolerance at 2.86%. The prevalence of DM was significantly higher in men (14.58%) than in women (7.13%, p<0.001), increased with age in both sexes and was more prevalent in hypertensive (p<0.001) and obese subjects (p=0.001) and in those living in rural areas (p=0.003). In the multiple logistic regression analysis, significant predictors of pre-diabetes and DM together were age, homeostasis model of assessment of insulin resistance (HOMA-IR), alcohol consumption and educational status, whereas those of DM alone were age, HOMA-IR and triglycerides. Extrapolating our data to the whole country, the age-adjusted prevalence of DM was estimated at 11.97% (men 13.98%, women 9.25%), clearly indicating a major public health problem.