Context: To the best of our knowledge, no study has examined the effects of vitamin D-calcium cosupplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient type 2 diabetics. Objective: This study was performed to assess the effects of vitamin D and calcium supplementation on inflammatory biomarkers and adipocytokines in vitamin D-insufficient people with type 2 diabetes. Methods: Totally, 118 diabetic patients were enrolled in this randomized, placebo-controlled clinical trial. After matching for age, sex, body mass index, type and dose of hypoglycemic agents, and duration of diabetes, subjects were randomly assigned into 4 groups receiving the following: 1) 50000 IU/wk vitamin D + calcium placebo; 2) 1000 mg/d calcium + vitamin D placebo; 3) 50 000 IU/wk vitamin D + 1000 mg/d calcium; or 4) vitamin D placebo + calcium placebo for 8 weeks. Blood sampling was done for the quantification of inflammatory biomarkers and adipocytokines at the study baseline and after 8 weeks of intervention. Results: Calcium (changes from baseline: -75±19 ng/ml, P = .01) and vitamin D alone (-56 ± 19 ng/mL, P = .01) and joint calcium-vitamin D supplementation (-92 ± 19 ng/mL, P = .01) resulted in a significant reduction in serum leptin levels compared with placebo (-9 ± 18 ng/mL). This was also the case for serum IL-6, such that calcium (-2 ± 1 pg/mL, P < .001) and vitamin D alone (-4 ± 1 pg/mL, P < .001) and their combination (-4 ± 1 pg/mL, P < .001) led to significant reductions compared with placebo (3 ± 1 pg/mL). After adjustment for potential confounders, individuals in the calcium (-3.1 ± 1.3, P < .05), vitamin D (-3.1 ± 1.3, P < .05), and joint calcium-vitamin D groups (-3.4 ± 1.3, P < .05) had greater reductions in serum TNF-α concentrations compared with placebo (0.1 ± 1.2). Individuals who received joint calcium-vitamin D supplements tended to have a decrease in serum high-sensitivity C-reactive protein levels compared with placebo after controlling for baseline levels (-1.14 ± 0.25 vs 0.02 ± 0.24 ng/mL, P = .09). Conclusion: Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-α concentrations in vitamin D-insufficient people with type 2 diabetes.