Individuals who regularly shift their sleep timing, like night and/or shift‐workers suffer from circadian desynchrony and are at risk of developing cardiometabolic diseases and cancer. Also, shift‐work is are suggested to be a risk factor for the development of mood disorders such as the burn out syndrome, anxiety, and depression. Experimental and clinical studies provide evidence that food intake restricted to the normal activity phase is a potent synchronizer for the circadian system and can prevent the detrimental health effects associated with circadian disruption. Here, we explored whether adult male Wistar rats exposed to an experimental model of shift‐work (W‐AL) developed depressive and/or anxiety‐like behaviors and whether this was associated with neuroinflammation in brain areas involved with mood regulation. We also tested whether time‐restricted feeding (TRF) to the active phase could ameliorate circadian disruption and therefore would prevent depressive and anxiety‐like behaviors as well as neuroinflammation. In male Wistar rats, W‐AL induced depressive‐like behavior characterized by hypoactivity and anhedonia and induced increased anxiety‐like behavior in the open field test. This was associated with increased number of glial fibrillary acidic protein and IBA‐1‐positive cells in the prefrontal cortex and basolateral amygdala. Moreover W‐AL caused morphological changes in the microglia in the CA3 area of the hippocampus indicating microglial activation. Importantly, TRF prevented behavioral changes and decreased neuroinflammation markers in the brain. Present results add up evidence about the importance that TRF in synchrony with the light–dark cycle can prevent neuroinflammation leading to healthy mood states in spite of circadian disruptive conditions. In male rats exposed to an experimental model of shift‐work, we reported circadian disruption, depressive and anxiety‐like behaviors as well as neuroinflammation in brain areas associated with mood regulation. Time‐restricted feeding associated with the normal activity phase prevents depressive and anxiety‐like behaviors as well as neuroinflammation.