Background: Vitamin D deficiency is markedly prevalent in children and adolescents with type 1 diabetes mellitus (T1DM). Despite accumulating evidence to support the link between vitamin D deficiency and both impaired glucose metabolism and altered immune responses in vitro and in vivo, it is not known whether vitamin D deficiency is linked to poor glycemic control and/or systemic levels of inflammatory cytokines in children and adolescents with T1DM. Aims: The purpose of this study was to examine the relationship between 25-hydroxyvitamin D (the functional indicator of vitamin D status) and HbA1c (the standardized index of glycemic control); and to determine whether inflammatory cytokines IL-6, IL-8, and IL-10 mediate this relationship in metabolically stable children and adolescents with T1DM. Methods: A cross-sectional design was used to examine these relationships in a convenience sample of 197 children and adolescents with T1DM 7-18 years, recruited from the Diabetes Center for Children at the Children’s Hospital of Philadelphia. Non-fasting serum levels of 25-hydroxyvitamin D, IL-6, IL-8, IL-10, and blood glucose were measured. Data on socio-demographic and disease-related variables including HbA1c were abstracted from medical records. Age- and sex-specific body mass index standard deviation scores (BMI z-score) were calculated. General linear modeling was used to examine the hypothesized relationships between primary variables, while controlling for select socio-demographic and disease-related covariates. Results: Mean HbA1c was 8.6±1.4%; 22.8% subjects had poor glycemic control. Mean 25-hydroxyvitamin D was 54.6±17.8nmol/L; 90.0% subjects had 25-hydroxyvitamin D levels less than 75nmol/L. Mean serum IL-6 was highest in overweight/obese adolescent females (1.57±1.29pg/ml). Mean serum IL-10 was highest in African Americans with poor glycemic control (15.2±22.5pg/ml). Serum levels of IL-8 were not detected in this sample. 25-hydroxyvitamin D was not associated with HbA1c (β=0.008; P=0.108), nor with IL-6 (β=-0.005; P=0.175) or IL-10 (β=0.004; P=0.356). IL-6 was not associated with HbA1c (β=0.09; P=0.418). IL-10 was significantly associated with HbA1c (β=0.21; P=0.008). Conclusions: In this study sample of metabolically stable children and adolescents with T1DM, neither 25-hydroxyvitamin D nor IL-6 were significantly associated with HbA1c. IL-10 was significantly associated with HbA1c. Clinical controlled trials are needed to confirm these results and assess the effect of varied doses of vitamin D supplements on inflammatory cytokines and ultimately measure the effect of inflammatory cytokines on HbA1c in T1DM.