It has been proposed that insulin resistance (IR) is associated with the development of Type 2 diabetes mellitus and cardiovascular disease. The aim of this study is to determine the prevalence of IR in Greek schoolchildren and to investigate factors associated with IR.Between October 2005 and March 2006, 522 children were recruited from Crete. Physical activity and dietary habits, anthropometric and biochemical characteristics, as well as medical history of pupils' parents were recorded. IR was estimated using the homeostasis model assessment (HOMA-IR), fasting glucose-to-insulin ratio (FGIR) and quantitative insulin sensitivity check index (QUICKI). Multiple linear regression was used to determine independent predictors for IR.Fasting insulin levels and HOMA-IR scores were higher in obese children and girls compared with their normal-weight peers (P < 0.001). Moreover, the former had lower values in FGIR and QUICKI indices compared with the latter, indicating that obese children and girls are more insulin resistant compared with their counterparts (P < 0.001). The prevalence of IR was 9.2% (2.9% in normal-weight, 10.5% in overweight and 31.0% in obese children), using as a threshold HOMA-IR > 2.10 97.5th percentile of normal-weight participants). Multiple linear regression revealed that central adiposity, female gender and intake of simple carbohydrates is associated positively with HOMA-IR values, even after controlling for many other factors.These findings demonstrate that girls and obese children, particularly those with central adiposity, are at high risk of developing IR. Therefore, these groups should be targets of Type 2 diabetes mellitus and cardiovascular disease preventive interventions.