Our study showed that, in the IDD rat model, the expression of DNMT1 was upregulated and, on the contrary, DNMT1 inhibition led to suppression of the progression of degenerative changes in NPCs and nucleus pulposus tissues via suppressing the M1 macrophage polarization and promoting the M2 macrophage polarization. Here, DNMT1 is linked to intervertebral disk degenerative disorder.