Objective · To clarify the therapeutic effect of ginsenoside Re on intervertebral disc degeneration (IDD) and the potential underlying mechanism. Methods · 10 ng/mL tumor necrosis factor-α (TNF-α) was used to stimulate nucleus pulposus (NP) cells. The expression of inflammation and cartilage-related genes, including matrix metalloproteinase 3 (Mmp 3), a disintegrin and metalloproteinase with thrombospondin 5 (Adamts 5), aggrecan and collagen typeⅡa1 (Col2a1), were measured and compared by real-time quantitative polymerase chain reaction with ginsenoside Re concentration varying from 12.5-50 μmol/L. After stimulation of NP cells with 10 ng/mL TNF-α, the amounts of nuclear factor-κB (NF-κB) pathway-related proteins were measured by using Western blotting with or without 50 μmol/L ginsenoside Re. Twelve 8-week-old rats were used to make coccyx degeneration models (coccygeal vertebrae 6/7 as sham, coccygeal vertebrae 7/8 as puncture), intraperitoneal injection of 50 μmol/L ginsenoside Re as treatment group (n=6) and phosphate buffered saline solution (PBS) as control group (n=6). One month later, the heights of the intervertebral discs were detected by X-ray. The rats' intervertebral disc NP tissues were observed by safranin O-fast green staining and hematoxylin-eosin staining, and histological grade was evaluated. By immunofluorescence, the expressions of TNF-α, MMP 3, aggrecan and COL2A1 were observed. Results · The expressions of inflammatory factors in the NP cells including Mmp 3 and Adamts 5 decreased and the expressions of aggrecan and Col2a1 increased under the treatment of 50 μmol/L ginsenoside Re (all P=0.000). Western blotting showed that compared with the NP cells only stimulated by TNF-α, the amounts of protein p-p65 and p-IκBα decreased significantly under the treatment of ginsenoside Re (both P=0.000). X-ray showed that compared with the puncture segment of PBS injection group, the puncture segment of ginsenoside Re injection group had better disc height indices (P=0.004) and degeneration grades (P=0.000). Immunofluorescence showed ginsenoside Re injection group expressed more aggrecan and COL2A1 (P=0.000), and less TNF-α and MMP 3 (P=0.000). Conclusion · GinsenosideRe can reduce the expressions of inflammatory factors by inhibiting NF-κB pathway in NP cells as well as maintain the disc heights and effectively alleviate the IDD level of rats.