ETHNOPHARMACOLOGICAL RELEVANCE: Genus Ceiba, (Malvaceae) encompasses 200 species that naturally thrive in tropical and subtropical regions worldwide as West Africa, South Asiam Mexico, Central America, South America, the Bahamas and the Caribbean. Ceiba speciosa (A.St.-Hil.) Ravenna (CS) and Ceiba insignis (Kunth) P.E.Gibbs & Semir (CI) were traditionally used for treatment of inflammatory disorders as ulcer, arthritis and rheumatism. AIM OF THE STUDY: The study aimed to characterize CS and CI leaves methanol extracts and to evaluate their antioxidant and anti-inflammatory effect on acetic acid induced ulcerative colitis in rat model. MATERIALS AND METHODS: Chemical profiling of CS and CI was done by liquid chromatography combined with mass spectrometry (LC-MS). In vivo ulcerative colitis model was induced by acetic acid. Histological examination and levels of inflammatory and oxidative stress markers were investigated. Docking studies were performed in the active sites of 5-LOX and COX-2 using Discovery studio software. RESULTS: Thirty phytoconstituents, mostly flavonoids and phenolic acids were characterized in CS and CI. Both extracts showed significant antioxidant and anti-inflammatory activity at the low and high doses (200 and 400 mg/kg p.o.) but CI exhibited better activity than CS. CI showed pronounced antioxidant activity evidenced by reduction in malonaldehyde levels (41.3 % and 48.6 %) with significant elevation in catalase by 2.6 and 3.1 folds and glutathione by 2.6 and 3.4 folds respectively. The anti-inflammatory activity reflected in the reduction of COX-2 levels (33.0-52.0 %), TNF-alpha (47.4-63.4 %) respectively. As for AMPK and NF-kB levels at the low dose, CI increased their levels significantly by 1.4 and 4.5 folds while at the high dose AMPK levels elevated by 6.7 folds. The docking experiment showed that clovamide had the best fitting within the 5-LOX and COX-2 active sites with binding energy (DeltaG = -35.8 and -36.6 kcal/mol) respectively. CONCLUSION: Both CS and CI showed potent anti-inflammatory activity that further consolidates its traditional importance in ulcerative colitis rat models, but CI showed more potency.