Adjuvant-induced arthritis is an animal model of chronic inflammation and rheumatoid arthritis. Chronic arthritis induces cachexia associated with an inhibition of the growth hormone (GH)-insulin-like growth factor-I (IGF-I) system together with an activation of the E3 ubiquitin ligase enzymes muscle atrophy F-box (atrogin-1) and muscle Ring finger 1 (MuRF-1) in the skeletal muscle. Muscle wasting is believed to accelerate morbidity and mortality in rheumatoid arthritis.The aim of this study was to analyzed the effect of GH and IGF-I administration on E3 ubiquitin ligase system in the gastrocnemius muscle of arthritic rats. Arthritis was induced in adult male Wistar rats by an intradermal injection in the sole of the right paw of 1 mg of complete Freund’s adjuvant. Fifteen days after adjuvant’s injection, 300 µg /kg of GH or 200 µg /kg of IGF were administrated by subcutaneous injection 18 and 3 hours before being humanly killed. Arthritis induces anorexia, for that reason we included a pair-fed group to discard a possible effect of decreased food intake. Gene expression of IGF-I and GH receptor in liver and ubiquitin ligase enzymes atrogin-1 and MuRF-1 in skeletal muscle were quantified using RT-PCR. Serum IGF-I was measured by radioimmunoassay (RIA). Arthritis decreased IGF-I and GH-receptor gene expression in liver (P<0.05), as well as circulating IGF-I levels (P<0.05). In skeletal muscle, arthritis increased atrogin-1 and MuRF-1 gene expression (P<0.01). These effects are not the result of anorexia, since in pair-fed group the expression of those genes was not modified. Exogenous GH administration increased liver IGF-I mRNA and serum IGF-I levels (P<0.05). In control, but not in arthritic rats, GH and IGF-I administration decreased atrogin-1 (P<0.05) and MuRF-1 gene expression (P<0.05). However, neither GH nor IGF-I administration were able to prevent arthritis-induced increase in atrogin-1 and MuRF-1 gene expression in the gastrocnemius muscle. Although the GH-IGF-I system has an inhibitory effect on ubiquitin ligase enzymes, by decreasing atrogin-1 and MuRF-1 gene expression, in arthritis the GH or IGF administration was not able to reduce the expression of these enzymes in the skeletal muscle.