Thymoquinone (TQ) is an active constituent in Nigella sativa, and is extensively reported for its distinguished antioxidant, and anti-in ammatory bioactivities. Despite the local protective response of the acute in ammation, it contributes to the development of various disease conditions such as cell death, organ damage, or genesis of tumors. Hence, in this study, the effects of orally administered TQ (50 and 100 mg/kg) for 14 days against edema development, oxidative stress, and in ammation were investigated in paw edema induced by carrageenan in mice. Indomethacin (10 mg/kg) was used as a reference drug. The results revealed that TQ reduced the paw edema volume in a time-dependent manner, attenuated acetic acid-provoked writhing movements, and reduced xylene-triggered ear edema.Hematological ndings revealed marked normalization of altered counts of WBCs, and platelets. Furthermore, paw tissue levels of MDA and NO showed marked decreases together with increases Nrf2, GSH, SOD, CAT, GPx, and GR after TQ administration. Additionally, TQ decreased the levels of proin ammatory mediators, such as IL-1b, TNF-α, IL-6, MCP-1, CRP, MPO, and NF-κB in the in amed paw tissue. Moreover, appreciable decreases were recorded in COX-2 and its product (PGE-2) as well as the immune reaction of TNF-α in TQ-treated mice. Histopathological ndings further validated the potential antioedematous, anti-in ammatory power of TQ in in amed tissues. Conclusively, the obtained ndings encourage the potent application of TQ to subside the acute in ammatory events because of its striking antioxidant and anti-in ammatory properties in the in amed paw tissue.