Abstract: Background: The present study is designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, since MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage.Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF) and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leave extract.Results and Conclusion: When their effects on MMP-13 expression were compared, the n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression against IL-1β-treated SW1353 cells (human chondrosarcoma), whereas the total extract and GTF did not. In particular, GDF/F4, the most prominent inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from IL-1α-treated rabbit cartilage culture (30.6% inhibition at 30 μg/ml). Therefore, it is suggested that some preparation from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as a new therapeutic agent.