Many studies of the etiology and intervention for obesity have gradually focused on the brain, trying to curb the occurrence of obesity from the source. Hypothalamic inflammation has been a concern and an unresolved scientific issue in the development of obesity. Studies have shown that hypothalamic inflammation not only impairs energy balance, but also increases obesity-related insulin and leptin resistance, further promotes peripheral tissues storing up fat cells, eventually leads to the development of obesity. In addition, hypothalamic inflammation occurs before weight-gain and peripheral tissue inflammation with high-fat diets. Therefore, more and more scholars believe that hypothalamic inflammation is an important cause of dietary-induced metabolic abnormalities. The occurrence of hypothalamic inflammation is mainly accompanied by a series of complex and rapidly-activated glial, including microglia, astrocytes, and tanycyte. These cells are responsible for maintaining hypothalamic metabolic homeostasis and making up the important components of the regulatory network. Moreover, multiple teams also found that a variety of weight-loss methods(e.g. bariatric surgery, targeted drugs, fecal microbiota transplantation, and so on) can improve hypothalamic inflammation levels. Therefore, it is important to understand the mechanism of hypothalamic inflammation through different neurons, which is expected to find a more effective and safer solution to intervene and treat obesity in the future.