Neuroinflammation is described as an inflammatory cascade in the nervous tissue that plays a pivotal role in various neurological disorders, including neurodegenerative diseases, central nervous system (CNS) injury, and infection(Welcome, 2020; Yang and Zhou, 2019). Emerging evidence suggest that neuroinflammation is mainly characterized by glial activation, inflammatory factor release, blood-brain barrier impairment, and recruitment of peripheral immune cells(Nelke et al., 2022; Ransohoff, 2016). The triggering receptor expressed by myeloid cell 2 (TREM2) is a key membrane protein receptor closely related to inflammation in the CNS. TREM2 is preferentially expressed in a subset of myeloid cells including microglia, dendritic cells, and tissue-specific macrophages (osteoclasts, Kupffer cells, macrophages in adipose tissue, alveoli, intestine, peritoneum, adrenal gland and placenta) (Colonna, 2023; Paloneva et al., 2003; Sharif et al., 2014; Xing et al., 2015). TREM2 can be activated by a wide range of endogenous and exogenous ligands, and regulates the proliferation, survival and apoptosis of these myeloid cells (Bouchon et al., 2001; Peng et al., 2023; Wu et al., 2015; Zhang and Chen, 2023; Zheng et al., 2017). It has been reported that TREM2 is associated to many neuroinflammatory diseases, including traumatic brain injury, stroke, Amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Multiple Sclerosis (MS) (Chen et al., 2020; Cignarella et al., 2020; Jericó et al., 2023; Liu et al., 2022; Saber et al., 2017; Wijeyekoon et al., 2020; Yan et al., 2022). Additionally, accumulating evidence suggests that in addition to microglial inflammation regulated by TREM2 through signaling pathways, TREM2-mediated microglial phagocytosis, metabolism, and autophagy are also involved in the regulation of neuroinflammation (Cao et al., 2022; Han et al., 2022; Jiang et al., 2014, 2016). However, the interaction between TREM2 in microglia and neuroinflammation, and the specific mechanisms involved have not been fully elucidated, warranting further investigation. In this review, we summarize the role of TREM2-mediated microglia in modulating neuroinflammation, reveal the underlying mechanisms, and provide a theoretical basis for the development of new TREM2-targeted therapies for neuroinflammation.