OBJECTIVE: To investigate how inflammation after spinal cord injury affects the apoptotic process in neu-ron glial cells and to investigate the antioxidative effect of hesperidin in developing inflammation. STUDY DESIGN: Twenty Wistar Albino rats were categorized as control and SCI group. At T10-T11 vertebras, a steel rod was dropped from 10 cm to create a spinal cord injury under anesthesia. A cylindrical tube of 10 cm length was fixed to the area to undergo laminectomy. Spinal damage was created by dropping a 15-g metal weight down the tube. Immediately after the trauma, 30 mg/kg hesperidin was administered for 7 days. At the end of experiment, blood samples were taken from the animals and analyzed with various bio-chemical markers. The spinal cord was excised for routine paraffin tissue protocol. Hematoxylineosin stain was used for histological examination, and APAF-1 and NF-kappa B anti bodies were used for immunohistochemistry. RESULTS: Both MDA and MPO values were increased in the SCI group as compared to the control and SCI+ Hesperidin groups, and the increase was statistically significant. GSH content was decreased in the SCI group as compared to the control and SCI+ Hesperidin groups, and the decrease was statistically significant. In the SCI group, some of the ependymal cells were degenerative and hyperplastic, degeneration and pyk-nosis in the nuclei of neurons in the substantia grisea region, and loss of structural integrity in the exten-sions were observed. In the SCI+ Hesperidin group, mild degeneration of the ependymal cells, some of the neurons in substantia grisea continued to have an apoptotic appearance, while the integrity of the neuron cytoplasm and nucleus was preserved. In the SCI group, APAF-1 expression was positive in some of the ependymal cells. APAF-1 expression was weak in neu-ron structures and glial cells in the substantia alba and substantia grisea region in the SCI+ Hesperidin group. After SCI, there was a significant increase in NF-kappa B expression in endothelial cells and perivascular glial cells and degenerated neurons. In the SCI+Hesperidin group, mild NF-kappa B expression was observed in glial cells, some neu rons in the substantia grisea and sub-stantia alba region, and blood vessel endothelial cells. CONCLUSION: Hesperidin administration after spinal cord injury was thought to inhibit neuronal cell apo-ptosis (APAF-1) by reducing oxidative stress, inflamma-tory mediators, and NF-kappa B.