An inverse correlation between the morbidity of rheumatoid arthritis and daily intake of β-cryptoxanthin has been epidemiologically shown. In this study, we investigated the effects of β-cryptoxanthin on the metabolism of cartilage extracellular matrix in vivo and in vitro. Oral administration of β-cryptoxanthin (0.1-1 mg/kg) to antigen-induced arthritic rats suppressed the loss of glycosaminoglycans in articular cartilage, which is accompanied by the interference of aggrecanase-mediated degradation of aggrecan. Inhibition of the interleukin 1α (IL-1α)-induced aggrecan degradation by β-cryptoxanthin was also observed with porcine articular cartilage explants in culture. β-Cryptoxanthin (1-10 μM) dose-dependently down-regulated the IL-1α-induced gene expression of aggrecanase 1 (ADAMTS-4) and aggrecanase 2 (ADAMTS-5) in cultured human chondrocytes. Moreover, β-cryptoxanthin was found to augment the gene expression of aggrecan core protein in chondrocytes. These results provide novel evidence that β-cryptoxanthin exerts anti-arthritic actions and suggest that β-cryptoxanthin may be useful in blocking the progression of rheumatoid arthritis and osteoarthritis.