Although evidence shows that intervertebral disc degeneration is generally characterized by angiogenesis, the role of angiopoietin has not been investigated. This study examined the presence of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) within the native intervertebral disc (IVD) and elucidated their functions in the regulation of nucleus pulposus (NP) cells. Initial investigation of uncultured NP tissue revealed that Ang-1 and Ang-2 were expressed by native NP cells. Ang-2 expression was significantly increased in infiltrated and degenerate samples relative to normal samples. The ratio of Ang-2/Ang-1 in tissues from patients increased markedly with increasing age and level of degeneration of the IVD. The ratio of both Ang-2/Ang-1 mRNA and protein increased over time when cells were subjected to constant pressure at 1 Mpa in vitro. Our findings indicate that Ang-2 plays a role in suppressing cell adhesion and viability, and promotes the apoptosis of NP cells and that Ang-2 can inhibit the pathways stimulated by Ang-1 and fibronectin. Ang-2 release during IVD degeneration causes higher ratio of Ang-2 to Ang-1, further inhibits NP cell viability and adhesion, promoting apoptosis by blocking PI3K/Akt signaling. The present study therefore provides new insights into the role of the angiopoietin-Tie system in the pathogenesis of IVD degeneration.