Insufficient evidence exists regarding the effect of nanoparticles, particularly liposomes loaded with a statin, on traumatic brain injury (TBI). We investigated the impact of atorvastatin-loaded PEG (polyethylene glycol) conjugated liposomes (LipoStatin) on outcomes in mice with TBI. PEGylated liposomes loaded with atorvastatin were developed as nanoparticles to specifically accumulate in the injury region and release the drug to lessen the harmful effects of TBI. TBI was induced using the Marmarou method, applying five consecutive head impacts at 12-hour intervals with a weight of 120 g for each mouse. LipoStatin was administered 1 hour after TBI (LipoStatin group). LipoStatin efficiently accumulated at the TBI site in mice. Evaluations for IL-6 and eNOS mRNA expression levels at five days after TBI revealed significant anti-inflammatory effects of LipoStatin. The IL-6 levels of the TBI decreased in both the statin (7.3 fold, p=0.0152) and the LipoStatin (23 fold, p=0.0022) groups, compared to the control in RT-PCR. At five days, protein expression of Claudin-5, occludin (p=0.0260), JAM-A, and Caveolin-1 (p=0.0152) by western blot showed considerable recovery of blood-brain barrier (BBB) breakdown by LipoStatin. In addition, the LipoStatin group exhibited significantly lower BBB disruption by TBI than the control group, assessed by a fluorescence preclinical imaging system for Evans blue leakage (control vs LipoStatin p=0.0001). PEGylated LipoStatin may more effectively deliver statin to the injured brain and could have significant neuroprotective effects. Thus, PEGylated LipoStatin shows promise as a targeted therapy for TBI and other major vascular diseases.