Ossification of Ligamentum Flavum (OLF) is associated with serious neurologic symptoms including thoracic myelopathy and spinal stenosis. The pathogenesis of thoracic OLF is mainly due to the localized mechanical stress on the ligament induced enchondral ossification. However, despite numerous epidemiological and basic science studies, the mechanism of this process remains unclear. Studies have suggested that inflammatory cytokines, such as IL-6, TNF-α, seem to play a crucial role in OLF. In this review, we summarise the mechanistic information on the roles of inflammation cytokines in OLF and discuss about several therapeutic methods for OLF. Further studies on the role of cytokines in OLF should provide important insights into the designation of therapeutic strategies in preventing human spinal stenosis caused by OLF.