Background: Prevention of primary damage caused by head trauma may be avoided with protective measures and techniques which is a public health concern. Experimental and clinical studies about treatment of head trauma were all centered to prevent secondary damage caused by physiopathological changes following primary injury. Neuroprotective features of tetracyclines were the focus of several experimental studies in the last decade. In the present study we aimed to investigate the neuroprotective effects of tetracycline in an experimental model of blunt brain injury in rats. Materials and Methods: 32 male Sprague-Dawley rats were divided into four experimental groups (n = 8). Head trauma was not performed in control group (group 1, craniectomy only). In the second group, head trauma and craniectomy were performed. Intraperitoneal saline was used in addition to trauma and craniectomy for treatment in group 3 whereas intraperitoneal tetracycline and saline were used for treatment in group 4. Results: When histological examinations performed by transmission electron microscopy were evaluated, injury at ultrastructural level was demonstrated to be less pronounced in tetracycline group with decreased lipid peroxidation levels. Conclusion: In accordance with these findings, we conclude that systemic tetracycline administration is effective in reduction of secondary brain damage and brain edema and thus it may be considered as a therapeutic option.