Objective: The present study was designed to investigate the anti-colitic effect of Proanthocyanidins (Pcs) on acetic acid -induced ulcerative colitis in rats. Methods: Forty male rats (220-250 g) were divided into five equal groups. Group Ι:(Control normal group) rats received no drugs. Group Π: (Early UC-induced group) rats received 3% acetic acid (2ml/rat) intracolonially and sacrificed 3 days later from induction. Group III:(Late UC –induced group) rats received acetic acid similar to group 2 and sacrificed after 21 days. Group IV:(Early UC+Pcs protected group) rats received Pcs (200 mg/kg body weight/day) orally for 21 days prior to acetic acid administration for UC induction. Group V:(Late UC+Pcs treated group) treated with Pcs as in group III for 21 days after UC induction. Results: A significant increase in L-MDA and MOP with marked decrease in GSH and CAT activity in colon of acetic acid -induced colitis in rats as compared with control group. However, a significant depletion of colon tissue L-MDA, MOP and marked increase in GSH and CAT activity were observed after Pcs treatment compared to ulcerated untreated rats. The qPCR results revealed a significant upregulation of mRNA gene expression levels of TNF-α, COX-2 and a significant downregulation in TGF-β1 in colon of acetic acid -induced UC in rats. The expression levels of TNF-α, COX-2 was significantly downregulated and a significant upregulated in TGF-β1 in colon tissues after administration of Pcs. Conclusions: Proanthocyanidins protects rats colon mucosa damage against acetic acid -induced ulcerative colitis via anti-inflammatory and anti-oxidative mechanisms.