Abstract Synthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited either by Toll-Like Receptor (TLR) dependent or independent immune stimuli. Although initially identified by their ability to block CpG-induced immune activation, it was shown that suppressive ODN was able to block multiple forms of immune stimulation and to be effective in the prevention and treatment of pathologic autoimmune and autoinflammatory diseases. Endotoxin-induced uveitis (EIU) is an established animal model of acute ocular inflammation. It is induced by either systemic or intravitreal administration of lipopolysaccharide (LPS). Familial Mediaterranean Fever (FMF) is an autosomal recessive periodic fever disease characterized by recurrent, self-limiting, febrile, inflammatory attacks of the serosal membranes such as peritoneum, pleura, and synovia. Present study aims to demonstrate the downregulatory effect of the suppressive DNA on EIU and FMF as local autoimmune and systemic autoinflammatory diseases respectively. Results indicated that LPS induced EIU in mice, A151 treatment strongly downregulated either expression or protein levels of IL6, IP10, IL1β, MIP1β, MIP3a or iNOS. Moreover, FMF patient PBMCs were more responsive to TLR ligand stimulation compared to healthy subjects and A151 strongly reversed this activation and suppressed several key Th1-cytokine/chemokine levels