Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that has anti-inflammatory and anti-cachetic actions. The aim of this work was to elucidate whether EPA administration is able to prevent arthritis-induced decrease in body weight and muscle wasting in rats. Arthritis was induced by intradermal injection of Freund's adjuvant; 3 days later 9 rats received 1g/kg EPA or coconut-oil daily. All rats were killed 15 days after adjuvant injection. EPA administration decreased the external signs of arthritis, paw volume as well as liver TNF- mRNA. EPA did not modify arthritis-induced decrease in food intake or body weight gain. However, EPA treatment prevented arthritis-induced increase in muscle TNF- and atrogin-1, whereas it attenuated the decrease in gastrocnemius weight and the increase in MuRF1 mRNA. Arthritis did not only decrease myogenic regulatory factors, but it increased PCNA, MyoD and myogenin mRNA in the gastrocnemius. Western blot analysis showed that changes in protein content followed the pattern seen with mRNA. In the control rats EPA administration increased PCNA and MyoD mRNA and protein. In arthritic rats, EPA did not modify the stimulatory effect of arthritis on these myogenic regulatory factors. The results suggest that in experimental arthritis, in addition to its anti-inflammatory effect, EPA treatment attenuates muscle wasting by decreasing atrogin-1 and MuRF1 gene expression and increasing the transcription factors that regulate myogenesis.