The present study was designed to investigate the anti-colitic effect of Proanthocyanidins (Pcs) in acetic acid -induced ulcerative colitis in rats.Forty male albino rats (220-250 g) were divided into five equal groups of 8 rats each. Group I: (Control normal group) rats received no drugs. Group II: (Early ulcerative colitis-induced group): rats received 2 ml (3% v/v) glacial acetic acid intracolonially at 21th day from experiment and sacrificed 3 days later of acetic acid administration. Group III: (Late ulcerative colitis-induced group) rats received glacial acetic acid similar to group II for 3 successive days and sacrificed after 21 days. Group IV: (Early ulcerative colitis + Proanthocyanidins protected group) rats received Proanthocyanidins (200 mg/kg body weight/day) orally for 21 days prior to glacial acetic acid administration for 3 days, then the animals were sacrificed. Group V: (Late ulcerative colitis + Proanthocyanidins treated group) rats first administered with glacial acetic acid then after 3 days Proanthocyanidins was administered for 21 days. A significant increase in L-Malondialdehyde (L-MDA) and Myeloperoxidase (MOP) activity with marked decrease in reduced glutathione (GSH) and Catalase (CAT) activity in colon tissue of UC-induced rats as compared with control normal group. However, a significant depletion of colon tissue L-MDA, MOP activity and marked increase in GSH concentrations and CAT activity were observed after Proanthocyanidins treatment compared to ulcerated untreated rats. The quantification real time PCR (qPCR) results revealed a significant up-regulation of mRNA gene expression levels of Tumor necrosis factor alpha (TNF-α), Cyclooxygenase-2 (COX-2) and a significant down-regulation in Transforming growth factor -β1 (TGF-β1) in colon of acetic acid -induced colon ulcer in rats. The expression levels of TNF-α, COX-2 were significantly down-regulated and a significant up-regulated in TGF-β1 in colon tissues after administration of Pcs. Proanthocyanidins (Pcs) protect rats colon mucosa damage against acetic acid -induced ulcerative colitis via anti-inflammatory and anti-oxidative mechanisms.