BACKGROUND: Current management of traumatic brain injury (TBI) is primarily directed toward preventing secondary brain injury, while specific pharmacological therapies targeting post-traumatic neuroinflammation remain limited. Bioactive constituents of Nigella sativa, particularly thymoquinone, have demonstrated anti-inflammatory and antioxidant properties that may modulate mechanisms involved in secondary brain injury. This study was conducted to evaluate the effects of oral N. sativa oil on serum interleukin (IL)-1β and IL-10 levels as inflammatory parameters, neurological function and necrosis in a rat model of TBI.METHODS: Sixteen male Wistar rats underwent Marmarou weight-drop TBI and were randomly assigned into two groups given either oral N. sativa oil or distilled water (n=8/group) for 7 days. Serum IL-1β and IL-10 concentrations were measured using rat-specific enzyme-linked immunosorbent assays (ELISA), and neurological function was assessed using the modified Neurological Severity Score (mNSS) at post-injury baseline and on treatment day-1, -3, and -7. After day-7, brain tissue was examined using hematoxylin–eosin (H&E) staining, and necrotic-cell count was assessed.RESULTS: IL-1β concentrations were significantly lower in the N. sativa group from day-1 onward, whereas IL-10 concentrations were significantly higher and mNSS scores were significantly lower from day-3 onward. By day-3, all three outcomes differed significantly: lower IL-1β (56.38±10.21 vs. 111.98±47.64 pg/mL; p=0.013), higher IL-10 (102.38±33.42 vs. 40.20±6.02 pg/mL; p=0.001), and lower mNSS (median: 4 (3-5) vs. 5 (5-6); p=0.003) than placebo group. These differences persisted through day-7, which also supported by lower necrotic-cell counts in the N. sativa group (3164.13±771.38 vs. 4028.38±204.58; p=0.008).CONCLUSION: Administration of oral N. sativa oil shifted the circulating cytokine profile toward an anti-inflammatory pattern and was accompanied by better neurological function and fewer neuronal necrosis after TBI. These findings suggest that N. sativa oil may have beneficial effect on neuroinflammation after TBI.KEYWORDS: Nigella sativa, traumatic brain injury, interleukin-1 beta, interleukin-10, neuroinflammation, modified Neurological Severity Score