Objective: Investigate the role of homocysteine (Hcy), Th17-related cytokines, and adhesion molecules in the inflammatory state seen in the sickle cell anemia (SCA). Methods: We studied the Hcy, interleukin (IL)-17, and transforming growth factor β (TGF-β) cytokine levels of 62 SCA patients, as well as the expression levels of inflammatory and endothelial activation markers. Results: We found significant associations between Hcy levels and increased expression of IL-17 and TGF-β among SCA patients, and a positive significant correlation between Hcy and soluble vascular cellular adhesion molecules (sVCAM). SCA individuals had raised IL-17 levels when compared with controls. Discussion: These results suggest a possible role of Hyc in the induction of TGF-β and IL-17. Other authors proposed that Hcy may contribute to the initiation and progression of vascular disease by monocyte activation, resulting in the secretion of cytokines that amplify the inflammatory response. The role of Hcy in cytokine production and oxidative stress in the endothelium may explain the increase of sVCAM expression and, the vascular activation currently described among the SCA individuals with the highest Hcy serum levels. The chronic inflammation was observed in hyperhomocysteinemic mice, with an increased expression of VCAM-1 and plasma levels of tumor necrosis factor-alpha, showing an association of this inflammatory molecule and vascular changes. Conclusion: Our findings suggest that the increased levels of IL-17,Hcy and sVCAM contributes contributes to the vascular inflammation and activation presented by SCA patients, which probably have an important role in vaso-occlusion. On the basis of the presented data, IL-17 and Hcy might be considered as important components in the pathogenesis of SCA.