Erythropoietin (EPO) as a major stimulator of red blood cell (RBC) production play a key role on brain protection and have a caring effect on neurons from hypoxic or traumatic injury. The objective of this trial was to study the safety and efficacy of recombinant human EPO (rhEPO) on level of consciousness and other outcomes in patient with post traumatic diffuse axonal injury (PTDAI).In a controlled double-blind randomized clinical trial, 54 patients aged 20-47 years were randomly allocated to 2 groups. Subjects in intervention group (n = 27) received 2000U open-label rhEPO (Erythropoietin-ß; Roche, Gren-zach-Wyhlen, Germany) subcutaneously for six doses in two weeks (on days: 2, 4, 6, 8 and 10). The efficacies of the intervention were evaluated by GCS (Glasgow Coma Scale) and GOS (Glasgow Outcome Scale).The patients that were treated by rhEPO improved earlier with the difference between the treatment groups occurring on the day 10 (score differences of 9.6 for GCS and 1.9 for GOS). The better course of the rhEPO-treated patients continued throughout the remaining study period. The hematocrit and red blood cell counts did not increase to levels exceeding the normal range in rhEPO patients.Intravenous EPO was well tolerated in diffuse axonal injury and was associated with an improvement in patients' outcome in 2 weeks.