Skeletal muscle weakness debilitates persons with rheumatoid arthritis (RA) and contributes to decreased quality of life for the afflicted patients. Oxidative stress is thought to be part of the pathophysiology of RA and we recently mapped specific oxidative posttranslational modifications (oxPTMs) on muscle actin (α-actin) that promote muscle weakness in mice and patients with RA. Specifically, we found oxPTMs 3-nitrotyrosine (3-NT) and malondialdehyde (MDA) adducts in three distinct regions of α-actin from mice and patients with RA. 3-NT and MDA are oxPTMs induced by free radical species superoxide (O2-) and peroxynitritite (ONOO-). Up until now, the intramuscular redox signalling in RA, including the interplay between sources of O2-/ONOO- and free radical scavengers is still unclear. Here we aim to elucidate the intramuscular redox signalling that contributes to skeletal muscle weakness in inflammatory conditions. Gene expression analysis by qRT-PCR showed a significant lower gene expression of ROS scavengers, including NQO1, catalase (CAT), SOD2 and GPx1 (n= 6; p< 0.05; two-tailed t-test) in skeletal muscle of mice with complete freund’s adjuvant (CFA)-induced arthritis than in healthy controls (Ctrl). SOD2/CAT scavenge O2- that can be produced by the mitochondria. Immunofluorescence staining shows a distinct striated CAT pattern every 1.83 µm and muscle fibres from mice with CFA-induced arthritis show an increased band width of the CAT protein (Ctrl= 0.69 ± 0.04 µm; CFA= 0.87 ± 0.05 µm; n=20; p< 0.05; two-tailed t-test). Experiments are now being performed with genetically-encoded redox-sensitive GFP probes specifically targeting mitochondria in order to quantify mitochondrial free radical production over time in muscle of mice with arthritis and healthy controls. Moreover, intraperitoneal injection of the CAT/ SOD2 mimetic EUK-134 restored muscle force in mice with arthritis to the level of healthy control mice (Ctrl= 477 ± 14 kN/m2; CFA 389 ± 26 kN/m2; CFAEUK-134 520 ± 25 kN/m2, mean ±SEM; n=5-6), which is in accordance with our previously published data from rats with arthritis. In summary, we show altered gene expression and localisation of ROS scavengers in muscles from mice with arthritis. In addition, treatment with targeted antioxidant EUK-134 improved muscle force in these mice. This implies that the ROS scavenging capacity is altered which can contribute to oxidative stress and muscle weakness in RA. All animal and human experiments were approved by the Swedish national and local ethical boards. Arthritis in mice was induced under anaesthetic conditions (2.5% induction – 4% maintenance).