The aim of this study was to evaluate the therapeutic potential of oxidative stress (OS) reduction by using pyridoindole (PI) antioxidants in adjuvant arthritis (AA). The substances tested were stobadine dipalmitate (STB) and SMe1. AA was used as animal model. The experiments included healthy animals, control arthritic animals and arthritic animals with administration of PI in the oral daily dose of 15 mg/kg b.w. during 28 experimental days. Biochemical parameters were determined on day 28. The volumes of hind paws (HPV) and animal body mass (BM) were measured every week. The effect of PI administration was evaluated on the basis of parameters of (a) inflammation (activity of GGT in spleen and hind paw joint homogenates), (b) arthritis (HPW, BM), and (c) OS (levels of TBARS and of HNE- and MDA-protein adducts in plasma). PI significantly increased the BM of animals and corrected the HPW. STB also significantly decreased the activity of GGT in joint homogenates. SMe1 was more effective in decreasing plasmatic TBARS levels, but the order of potency on the HNE- and MDA-protein adducts in plasma was different- STB was more effective than SMe1. Our results showed that the reduction of OS in arthritis also improved the clinical manifestations of the disease and decreased the inflammation (GGT). Moreover, in a pilot study we tested the STB in combination with methotrexate for AA treatment. Adition of STB increased the efficacy of methotrexate treatment established also by improvement of neutrophil‘s functionality, assessed by phagocytosis and metabolic activity