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A growing literature indicates that mitochondria are key participants in immune responses. Mitochondrial electron transport through oxidative phosphorylation machinery is an important source of cellular reactive oxygen species (ROS). Mitochondrial ROS are increasingly recognized as key regulator NFκB, MAPKs, and IRF signaling pathways and therefore influence immune responses. In this work, the feasibility of mitochondria targeted antioxidant SkQ1based therapy for prevention ocular inflammation was demonstrated in vivo. Here we investigated the antiinflammatory effect of SkQ1 on widely used for evaluating potential ocular antiinflammatory compounds model of lipopolysaccharide (LPS)induced uveitis in rabbits. It has been reported that LPS caused release of proinflammatory factors, such as tumor necrosis factorα (TNFα) and interlekin6 (IL6). As crucial inflammation mediators, TNFα and IL6 stimulates acute phase reaction of inflammation by influencing on oxidative stress, prostaglandins (PG) formation, leukocyte infiltration into the anterior segment (AS). We evaluated the effect of SkQ1 on ocular inflammation. At 24h after LPS injection, severe iris hyperemia and fibrinous pupillary membranes were observed. Compared to the LPS group SkQ1 pretreatment animals showed mild hyperemia and clear pupils. The histopathological changes in the AS of eyes were examined. Our results indicated in the LPS group histological evaluation revealed massive leukocyte infiltration into the AS. In the SkQ1 group the infiltrated leukocytes significantly decreased. Biochemical analyses of the AS showed that SkQ1 decreased LPSinduced IL6, PGE2 and malondialdehyde production in the AS. In conclusion, SkQ1 prevents LPSinduced uveitis and the subsequent production of proinflammatory mediators, at least in part, by blocking mitochondrial ROS production. These effects may contribute to the SkQ1mediated preventive effects on intraocular inflammatory diseases such as acute uveitis.