Objectives The present study aimed to investigate the anti-inflammatory effects of vitamin D and resistance training in men with type 2 diabetes mellitus and vitamin D deficiency. Design This study was a randomized, placebo-controlled, double-blinded clinical trial. Trial registration code: IRCT20190204042621N1 Participants Forty-eight patients with type 2 diabetes aged 40-65 (from a total of 52 volunteers in Ardabil diabetes clinic) were randomly assigned to either the vitamin D supplementation with resistance training group (VD + RT: n = 12), the resistance training group (RT: n = 12), the vitamin D supplementation group (VD: n = 12), or the control group (CON: n = 12). Intervention The subjects in VD group took vitamin D supplements at 50000 IU per 2 weeks for 3 months; the subjects in RT group exercised 3 times per week for 12 weeks; and the subjects in VD + RT group participated in both treatments. Subjects in CON group were asked to maintain normal daily life pattern for the duration of the study. Measurements Serum Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) and C-reactive protein (CRP) levels were determined at pre and post-test and the data were compared among the four groups and between two tests (4 × 2) using two-way ANOVA with repeated measures. Results IL-6 decreased significantly (P = 0.001) in all groups (VD + RT = %-71.73, RT = %-65.85, VD = %-61.70). TNF-α decreased significantly (P = 0.001) in VD + RT (%-44.90) and RT (%-40) groups. CRP showed no significant change in any group (P > 0.05). Conclusion Results demonstrated that vitamin D supplementation in addition to resistance training had positive effects on some inflammatory markers in T2D and vitamin D deficient men. Vitamin D supplementation was especially effective when it was complemented with exercise training.