Literatures indicate that microRNA-129-5p (miR-129-5p) or Fas-associated death domain (FADD) is related to intervertebral disc degeneration (IDD), but the effect of miR-129-5p/FADD axis on IDD is not studied. The study aimed to investigate whether miR-129-5p influenced immune privilege and nucleus pulposus (NP) cell apoptosis in rats with IDD via regulating FADD.A rat model with caudal IDD was established, and injected with miR-129-5p agomir or miR-129-5p antagomir to figure out the character of miR-129-5p in the cell apoptosis and inflammation in the nucleus pulposus (NP) tissues of IDD rats. NP cells were grouped as the same ways for determining proliferation, apoptosis, and senescence in NP cells of IDD rats. Annexin V-FITC/PI double staining detected the apoptosis of macrophages and CD8 cells co-cultured via transfected NP cells. Expression of miR-129-5p, FADD, collagen I, collagen II, aggrecan and Sox-9 in NP tissues and cells were determined.Up-regulated miR-129-5p decreased FADD, collagen I and elevated collagen Ⅱ, aggrecan, and Sox-9 in NP tissues and repressed inflammation in serum and NP tissues in IDD rats. Up-regulated miR-129-5p facilitated proliferation, inhibited senescence, apoptosis, and decreased FADD, collagen I and increased collagen Ⅱ, aggrecan, and Sox-9 in NP cells of IDD rats. Elevated miR-129-5p promoted the apoptosis of macrophages and CD8 cells.We pronounced that up-regulated miR-129-5p inhibited the apoptosis and facilitated the proliferation of NP cells, as well as the apoptosis of macrophages and CD8 cells via decreased FADD in IDD, suggesting that miR-129-5p had a protective effect on IDD.