Background Wallerian degeneration following nerve injury not only suppresses CD4 + T-cell responses but also promotes pro-inflammatory immunological responses through TNF-α and IL-1β. Recent research suggests that thymoquinone might enhance nerve recovery by exerting anti-inflammatory effects on both the innate and adaptive immune systems. This study aims to evaluate the effect of thymoquinone on neuroinflammation in a sciatic nerve crush injury, as represented by TNF-α, IL-1β, and the CD4+:CD8 + ratio.Methods In this study, 126 Wistar rats were divided into three main groups: placebo, thymoquinone 100 mg/kg, and thymoquinone 250 mg/kg administered daily. Rats were euthanised at six distinct time points: 12, 18, and 24 hours, as well as on day-5, day-6, and day-7. TNF-α and IL-1β levels were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA). The CD4+:CD8 + ratio in peripheral blood was determined via flow cytometry. Data analysis was conducted using MANOVA, Kruskal-Wallis, and Mann-Whitney U tests.Results No significant difference was noted in TNF-α levels between the treatment and placebo groups across all observation times. However, on day-6, the IL-1β level in the TQ 250mg/kg group was statistically lower than in the placebo group (p = 0.008). Furthermore, both the TQ 100mg/kg and 250mg/kg groups exhibited a higher CD4+:CD8 + ratio compared to the placebo group on day-5 (p = 0.007).Conclusion Daily TQ administration did not consistently reduce TNF-α and IL-1ß levels. However, both doses elevated the CD4+:CD8 + ratio during the early stages of Wallerian degeneration, suggesting a potential benefit of TQ on nerve regeneration.