It is well established that an obesogenic high-fat diet (HFD) causes brain inflammation, which eventually leads to obesity. Microglia are the resident brain immune cells, initiating local immune responses. In the brain, the mediobasal hypothalamus (MBH) plays a key role in sensing metabolic feedback and regulating energy homeostasis. HFD consumption stimulates microglial activity in the MBH, resulting in decreased numbers of the appetite-curbing pro-opiomelanocortin (POMC) neurons. In rats fed with a HFD, we observed that hypothalamic microglial cells are constantly activated, instead of showing daily rhythmicity, probably due to their constantly elevated 24-hour food consuming behavior. The goal of this study is to investigate whether a time-restricted HFD eating pattern influences the microglial activity, responsible for neuronal loss, in the MBH of male Wistar rats. To answer our research question, Wistar rats fed with a chow diet or HFD were divided into three groups, i.e. ad libitum, only light-phase feeding or only dark-phase feeding. After 4 weeks of HFD time-restricted feeding (TRF), the dark-feeding group showed a reduction in adiposity compared to the light-feeding and ad libitum group. Rats were sacrificed every 4 hours to profile hypothalamic microglial morphology. Interestingly, microglial cell numbers in the HFD dark-feeding group were less increased than in HFD ad libitum and light-feeding groups. In conclusion, our data suggest that HFD food intake restricted to the active period of the L/D cycle has beneficial metabolic outcomes, preventing obesity. Importantly, the microglial activity is affected by the timing of HFD food intake, as our data indicate less increased microglial cell numbers in HFD dark-feeding group compared to other groups. In the ongoing study, further investigation of MBH POMC neuronal loss will be performed in combination with studying the underlying intracellular signaling mechanisms.