ABSTRACT The methanol extract of Delonix regia bark (DMeOH) was investigated for its anti-inflammatory property in kappa-carrageenan (Carr)-induced hind paw edema of rats. DMeOH was orally administered and evaluated as a measure of edema, tissue destruction, and neutrophil migration to the inflammation site. The pro-inflammatory mediators, p-p65 subunit of NFκB, interleukin (IL)-1β, cycloxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed. Catalase (CAT) and superoxide dismutase (SOD) enzyme activity assays and malondialdehye (MDA) were quantified. The LC-MS fingerprint of the extract identified 10 polyphenols, of which five were structurally characterized based on their [M-H]− peak, UV-vis absorption compared to published data. Anti-inflammatory studies revealed that pre-treatment with DMeOH (0.5 g kg−1) prior to Carr-injection inhibited paw edema abating tissue destruction with decreased neutrophil infiltration. Carr-injection resulted in increased NO(•-) production, iNOS transcript and p-p65 subunit of NF-κB protein. DMeOH feed inhibited NO(•-) production and iNOS transcript levels. A decreased expression of NF-κB p-p65 subunit, COX-2 and IL-1β at 0.5 g kg−1 b.w oral feed suggest that DMeOH exerted its anti-inflammatory property by inhibiting NFκB activation. An increase in the antioxidant enzyme activities of CAT (78%) and SOD (49%) with reduced MDA levels was recorded.