ABSTRACT. Both rheumatoid arthritis (RA) and osteoarthritis (OA) are complex diseases. Studies and treatment of RA and OA have mainly focused on individual factors. However, there is still no clear understanding of their causes and adequate treatment alternatives are still being sought. We applied gene set-enrichment analysis to microarray datasets of RA and OA to look for regulatory mechanisms. We found 32 highly significant pathways, including 18 downregulated and 14 upregulated pathways associated with RA. We also identified 18 highly significant pathways, including 7 downregulated and 11 upregulated pathways associated with OA. Several such pathways were found in both RA and OA, including an upregulated PPAR signaling pathway and downregulated leukocyte transendothelial migration. Regulatory mechanisms in RA seem to be more complex than in OA. 3137This information could be useful for diagnosis and treatment of these two diseases.