Nitric oxide (NO) has recently been proposed as an important mediator in inflammatory phases and in loss of cartilage. In inflammatory arthritis NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factors such as cytokines and/or endotoxin. Neutrophils also play an important role in inflammatory reactions and the level of myeloperoxidase, a constituent of neutrophil granules, is related to the intensity of the inflammation. Because there is evidence that suggests that mud packs influence the main cytokines involved in cartilage damage, we tried to determine whether NO and myeloperoxidase are involved in the mechanisms of action of mud bath treatment. We enrolled 37 subjects and randomly assigned them to two groups: 19 patients underwent mud bath treatment (group A) while 18 patients underwent bath treatment alone. Blood samples were obtained before and after the treatment cycles to assay serum levels of NO, myeloperoxidase (MPO) and glutathione (GSH)-peroxidase. The results showed a statistically significant decrease in NO and myeloperoxidase serum values in groups A and B, while GSH-peroxidase was not significantly increase in either of the groups; no correlation was found between NO, myeloperoxidase and GSH-peroxidase serum values. Mud bath treatment can exert beneficial effects on cartilage homeostasis and inflammatory reactions, influencing NO and decreasing myeloperoxidase serum values. The increase in GSH-peroxidase was not correlated with the reduction of other biochemical markers, suggesting that mud bath treatment has different mechanisms of action.