ABSTRACT: Background:To evaluate the effect of vitamin D supplementation on C-reactive protein (CRP) through a systematic review and meta-analysis of randomized control trials (RCTs). Methods:PubMed-Medline, SCOPUS, Google Scholar and Web of Science databases were searched (up until April 2016) to identify RCTs evaluating the impact of vitamin D supplementation on CRP. We used random effects models (using DerSimonian-Laird method) as well as the generic inverse variance methods for quantitative data synthesis. For sensitivity analysis, we applied leave-one-out approach. To examine the heterogeneity we used I2 index. Registration code: CRD42016036932. Results:Among 1274 search items, 24 studies met the inclusion criteria in the final evaluation. Pooling the data together indicated a non-significant decrease in CRP level following administration of vitamin D (weighted mean difference [WMD] -0.26(mg/l), (95% CI -0.75 to 0.22, N?=?26 arms, heterogeneity p?=?0.042; I2 54.2%). The WMDs for IL6 was 0.67 pg/ml, (95% CI 0.29 to 1.06, N?=?16 arms, heterogeneity p?=?0.234; I2 19.1%), 0.43 pg/ml, (95% CI 0.08 to 1.05, N?=?26 arms, heterogeneity p?=?0.120; I2 42.1%), for IL10, and -0.11 pg/ml, (95% CI -0.53 to 0.30, N?=?12 arms, heterogeneity p?=?0.423; I2 9.2%) for TNF-?, 4.03 pg/ml, (95% CI 3.50 to 4.57, N?=?3 arms, heterogeneity p?=?0.752; I2 8.1%) for adiponectin. Sensitivity analyses confirmed the robustness of the findings. Conclusions:This study provided evidence that vitamin D supplementation had no impact on serum CRP, IL10, and TNF-?, while significantly increased serum IL6. We recommend RCTs with longer period of follow-up time (12 months) for future studies to provide explicit results.