Hypovitaminosis D is associated with an increased prevalence of diabetes mellitus type 2 (DMT2) and the metabolic syndrome. The purpose of this study was to examine the association between 25-hydroxy-vitamin D (25-OH-VitD) levels and adipocytokines and other indices of insulin resistance in a Saudi population with DMT2. One-hundred and fifty-five male and female Saudi adults aged 2680 were randomly selected from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort). Subjects were clinically assessed, anthropometry was obtained and serum 25-OH-VitD, leptin, adiponectin, resistin, insulin, CRP, TNF-α, glucose, triglycerides, total cholesterol, LDL, and HDL concentrations were measured. Results showed a negative correlation between 25-OH-VitD and BMI, LDL and glucose and a positive correlation between 25-OH-VitD and adiponectin, which remained significant after controlling for BMI. Thus, 25-OH-VitD serum levels are negatively correlated with adiposity, insulin resistance, and LDL levels in Saudi patients with DMT2. These results, together with the observed positive association between adiponectin and 25-OH-VitD suggest a role for this hormone as a link between 25-OH-VitD and insulin resistance and a possible beneficial effect of 25-OH-VitD on cardiovascular pathology.