Neuroinflammation is a complex process triggered by various factors such as injury, infection, oxidative stress, and other activators. In central immune system, microglia and astrocytes release a wide range of inflammatory mediators like cytokines and chemokines in response. Initially, acute neuroinflammation can have protective effects by promoting neuronal repair and maintaining homeostasis. However, chronic activation of neuroinflammation leads to excessive production of inflammatory mediators, resulting in neuronal dysfunction and degeneration. This can contribute to various neurological disorders, including Alzheimer"s disease (AD), Parkinson"s disease (PD), multiple sclerosis (MS), and Huntington"s disease (HD).In vitro cellular models are crucial for elucidating the underlying mechanisms of neuroinflammation. Investigating neuroinflammatory signaling pathways is essential for understanding the intricate network of molecules and cells involved. Key signaling pathways such as NF-κB, MAPK, PI3K/AKT, Nrf2/HO-1, and NLRP3 play critical roles in regulating neuroinflammation. During inflammation, activation of glial cells involves multiple signaling pathways simultaneously, primarily orchestrated by two key factors: MAPK and NF-κB. These pathways guide the inflammatory cascade, leading to the release of numerous inflammatory factors and reactive oxygen species (ROS). These inflammatory factors and ROS have dual effects. Firstly, they can directly harm neighboring neurons, promoting the accumulation of abnormal proteins and triggering neuronal apoptosis. Secondly, inflammatory factor receptors on cell membranes can initiate positive feedback loops that exacerbate the inflammatory response. Neuroinflammation encompasses various cell types within the central nervous system, forming a complex and interconnected malignant cycle. This ultimately culminates in irreversible brain damage. Moreover, innovative therapeutic approaches targeting specific signaling pathways and molecular targets show promise in treating diseases related to neuroinflammation.Various cellular models are commonly employed to investigate neuroinflammation, each focusing on different aspects: pathogen-related models involve substances like LPS (lipopolysaccharide), Aβ (amyloid beta), CpG-DNA, and viruses; cytokine models utilize IFN-γ (interferon-gamma); metabolic stress models include OGD (oxygen-glucose deprivation), MPP+ (1-methyl-4-phenylpyridinium), rotenone, and oxyhemoglobin; environmental toxin models encompass substances such as BPA (bisphenol A), PM2.5 (particulate matter), various metals, and nanoparticles; additive substance models involve alcohol, morphine, and METH (methamphetamine). Each model offers distinct advantages and drawbacks for studying neuroinflammation. In conclusion, research on these cellular models and their associated signaling pathways provides crucial insights into the mechanisms underlying neuroinflammation-related diseases. These insights are essential for developing effective therapeutic strategies and advancing clinical practice to address the complexities of neuroinflammatory diseases.