Chronic arthritis induces cachexia associated with an inhibition of the GH-IGF-I system and an activation of the E3 ubiquitin-ligating enzymes MAFbx and MuRF1 in the skeletal muscle. The aim of this work was to study the role of COX-2 in chronic arthritis-induced cachexia. Arthritis was induced in rats by Freund’s adjuvant injection, and the effect of two COX inhibitors; indomethacin, a nonspecific inhibitor, and meloxicam, a selective COX-2 inhibitor, on pituitary GH, and on liver and serum IGF-I levels were tested. Arthritis decreased body weight gain and GH and liver IGF-I gene expression. In the arthritic rats, both inhibitors, indomethacin and meloxicam, prevented the inhibitory effect of arthritis on body weight gain. Indomethacin and meloxicam administration to arthritic rats increased pituitary GH and liver IGF-I mRNA as well as serum levels of IGF-I. These data suggest that induction of COX-2 during chronic inflammation is involved in the inhibition of the GH-IGF-I axis and in the body weight loss. In the gastrocnemius muscle, arthritis increased the gene expression of TNF-, the E3 ubiquitin-ligating enzymes MAFbx and MuRF1 as well as of IGF-I and IGFBP-5. Inhibition of COX-2 by meloxicam administration increased gastrocnemius weight and decreased MAFbx, MuRF1, TNF- and IGFBP-5 gene expression. In summary, our data indicate that chronic arthritis-induced cachexia and muscle wasting are mediated by the COX-2 pathway resulting in a decreased GH-IGF-I secretion and increased expression of MAFbx and MuRF1 mRNA.