Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system(CNS), which is characterized by infiltration of immune cells, glia activation, demyelination and neurodegeneration. With the progression of MS, the peripheric infiltrated immune cells promote lymphocytes to locate in parenchyma or meninges adjacent to active lesions by secreting cytokines, such as C-X-C motif chemokine ligand (CXCL)13, CXCL12 and tumor necrosis factor-α(TNF-α), contributing to the formation of tertiary lymphoid structure (TLS). TLS formation in the CNS can directly trigger immune reaction independent from peripheral immune system, leading to the differentiation of pathogenic lymphocytes, the activation of microglia and astrocyte, and the recruitment of additional peripheral immune cells into the CNS by secreting proinflammatory cytokines and chemokines. The immune reaction in CNS caused by TLS leads to aggravated neuroinflammation and pathological changes, even irreversible neuron damage, which is thought to be responsible the progression of MS. The formation, distribution, tissue structure, and the mechanism of formation and distribution of the TLS in MS are reviewed in this article, which may contribute to potential therapeutic approaches for chronic progressive MS.