Background: Retinol-binding protein 4 (RBP4) is known to be involved in obesity-associated insulin resistance. Aims: To study the relationships between the degree of adiposity, insulin resistance indices, plasma lipids, inflammatory parameters, glucose intolerance (GI) status and plasma RBP4 levels in obese children and adolescents. Patients and Methods: Prospective study comprising 199 obese patients (95 boys) aged 8–16 years (11.8 ± 1.9). Fifty-three subjects (23 boys) of similar mean age, 11.3 ± 2.1 years, served as controls. BMI, waist and hip circumferences, plasma lipids, and inflammatory parameters were measured and patients underwent an oral glucose tolerance test. Plasma RBP4 levels were determined by nephelometry. Results: Plasma RBP4 levels (pg/ml) in obese patients with GI (n = 15) were higher (45.0 ± 14.1) compared with those of obese patients without GI (35.9 ± 11.7, p = 0.02; n = 184) and controls (31.5 ± 12.3, p = 0.04) in a generalized linear model adjusted for age, sex, BMI and pubertal status. A negative correlation was found between the skeletal muscle insulin resistance index and RBP4; positive correlations were found between the RBP4 and BMI Z-score (r = 0.213, p < 0.001), waist circumferences (r = 0.135, p < 0.05), plasma triglycerides (r = 0.187, p = 0.005) and apolipoprotein B (0.187, p = 0.007). Conclusions: Our results suggest a direct relationship between circulating insulin and RBP4 levels, which indicates that this protein might contribute to the development of muscle insulin resistance.