Traumatic brain injury (TBI) is accompanied by a disorder in cognitive, emotional, and behavioral functions without notable surface wounds after a physical impact to the head. Every year, 1.5 million people experience TBI from traffic accidents, falls, violence, and etc. currently, TBIs are classified into mild, moderate, and severe grades according to the consciousness status assessed by the Glasgow Coma Scale. In the case of mild TBI, injury in cranial nerves recovered after sufficient rest, however, it is difficult to expect a natural recovery in TBIs above the moderate level. Thus, molecular components involved in the recovery are deemed to be significantly different between mild TBI and moderate-to-severe TBI. Yet, studies that investigate what molecules or pathways are relevant to recovery phase of TBI are rare, especially for proteomic approaches. In this study, the prefrontal cortex tissues of mice undergone mild/severe TBI were collected over time periods of recovery, then their proteome were analyzed using LC-MS/MS. We performed quantitative analysis using 10-plex TMT, identifying about 300 proteins of which expression levels were temporally altered. We also discovered molecular pathways activated or inhibited under TBI condition through bioinformatics analysis. As a result, we found that the sirtuin signaling pathway was gradually inactivated over the phase of recovery and that the proteins involved in the lipid metabolism were stably up-regulated till two weeks from TBI. These findings will help to uncover molecular mechanisms leading recovery from TBI. Furthermore, the biomarkers that play important role in recovery of mild TBI can be used as a target of drug intervention intended to severe TBI patients.