Abstract Background: To the best of our knowledge, no study has examined the effects of vitamin D-calcium co-supplementation on inflammatory biomarkers and adipocytokines in vitamin D insufficient type 2 diabetics. 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. Materials and 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 four groups receiving: 1) 50000 IU/wk vitamin D + calcium placebo 2) 1000 mg/d calcium+vitamin D placebo 3) 50000 IU/wk vitamin D + 1000 mg/d calcium 4) vitamin D placebo+calcium placebo for 8 weeks. Blood sampling was done for quantification of inflammatory biomarkers and adipocytokines at study baseline and after 8 weeks of intervention. Results: Joint calcium-vitamin D supplementation resulted in a significant reduction in serum leptin (changes from baseline: -92±19 vs. -9±18 ng/mL in placebo, P=0.01), IL-6 (changes from baseline: -4±1 vs. -3±1 pg/mL in placebo, P<0.001) and TNF-alpha concentrations (changes from baseline: -3.4±1.3 vs. 0.1±1.2 pg/mL in placebo, P=0.04) compared with placebo. Individuals who only received calcium supplements tended to have a greater decrease in serum hs-CRP levels compared with placebo after controlling for baseline levels (changes from baseline: -0.07±0.25 vs. 0.02±0.24 ng/mL in placebo, P=0.09). Conclusion: Joint calcium-vitamin D supplementation might improve systemic inflammation through decreasing IL-6 and TNF-alpha concentrations in vitamin D insufficient people with type 2 diabetes.