Objective: This study was conducted to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU). Methods: This randomized, double-blind, placebo-controlled trial was performed among 60 patients with grade 3 DFU according to "Wagner-Meggitt's" criteria. Participants were randomly divided into two groups (each 30 participants) and received either 50,000 IU vitamin D supplements every 2 weeks for 12 weeks (group A) or placebo (group B). Fasting blood samples were taken at study baseline and after 12-week intervention to determine related markers. Results: After 12 weeks of intervention, compared with the placebo, vitamin D supplementation resulted in a significant reduction in ulcer length (-2.1 +/- 1.1 vs. -1.1 +/- 1.1 cm, P = 0.001), width (-2.0 +/- 1.2 vs. -1.1 +/- 1.0 cm, P = 0.02) and depth (-1.0 +/- 0.5 vs. -0.5 +/- 0.5 cm, P < 0.001), and erythema rate (100% vs. 80%, P = 0.01). In addition, in supplemented patients changes in serum insulin concentration (-3.4 +/- 9.2 vs. +2.8 +/- 93 mu IU/mL, P = 0.01), homeostasis model of assessment-estimated insulin resistance (-1.5 +/- 4.1 vs. +1.7 5.1, P = 0.01), the quantitative insulin sensitivity check index (+0.006 0.02 vs. -0.006 0.02, P = 0.03) and HbA1c (-0.6 +/- 0.6 vs. -0.1 +/- 0.5%, P = 0.004) were significantly different from those of patients in the placebo group. Additionally, following supplementation with vitamin D, significant reductions in serum total- (-15.8 +/- 18.9 vs. +5.3 +/- 31.8 mg/dL, P = 0.003), LDL- (-17.2 +/- 19.8 vs. +22 +/- 28.6 mg/dL, P = 0.003), total-/HDL-cholesterol ratio (-1.1 +/- 0.8 vs. -02 +/- 1.1, P = 0.001), high sensitivity C-reactive protein (hs-CRP) (-0.4 +/- 2.5 vs. +1.9 +/- 4.2 mu g/mL, P = 0.01), erythrocyte sedimentation rate (ESR) (-34.7 +/- 32.4 vs. -18.0 +/- 26.6 mm/h, P = 0.03) and plasma malondialdehyde (MDA) concentrations (-0.7 +/- 0.9 vs. -0.2 +/- 0.5 mu mol/L, P = 0.008) were seen compared with the placebo. Conclusions: Overall, vitamin D supplementation for 12 weeks among patients with DFU had beneficial effects on glucose homeostasis, total-, LDL-, total-/HDL-cholesterol, ESR, hs-CRP and MDA levels. In addition, vitamin D may have played an indirect role in wound healing due to its effect on improved glycemic control. (C) 2017 Elsevier Inc. All rights reserved.