Aim: Present study was elucidate the protective effect of pyridinone derivatives such as 7-amino-5-oxo-2- Phenyl-5H, 8H-dihydro-[1, 2, 4] triazolo [1, 5-α] pyridine - 6- carbonitril (TRP 1) by in vitro, in vivo and in silico.Methods: Radioligand binding assay was performed on human adenosine receptors (A2B) and assess A2B antagonist effect by adenylyl cyclase activity. In vitro study was carried out to determine the neutralize capacity against DPPH*, NO*, SO*, LPO* free radicals. TRP 1 at the doses 1 mg/kg bd.wt. and 10 mg/kg bd.wt p.o, was administered consecutively for 14 days in albino rats. Ulcerative colitis was induced with single dose of 2 ml of 3% acetic acid intrarectal on 14th day in treated rats. At the end of treatment, colonic tissue was collected and subjected for estimation of macroscopic score, glutathione, catalase, MPO and inflammatory parameters such as IL 1β, TNF α and IL 6. In silico study was carried out to evaluate the binding energy and IC50 toward IL 1β, TNF α and IL 6. Results: TRP 1 was antagonized the A2B receptors at the concentration of 30000 nM. In vitro study was revealed that TRP1 (1 mg/ml) was significantly neutralizes the free radicals of DPPH*, SO*, NO*and LPO*. In in vivo studies, intrarectal administration of acetic acid caused significantly (***P<0.001) increased macroscopic score, colon weight, colonic MPO, IL 6, IL 1β and TNF-α (*P<0.05), while TRP 1 treated colitis rats antioxidants system such as GSH (**P<0.01), catalase (*P<0.05) activity was significantly improved, decreases inflammatory mediators such TNF α (*P<0.05), IL 1β (**P<0.01) , IL 6 (**P< 0.01) and also suppresses the MPO activity (*P<0.05). In silico study was reported that the IC50 of TPR 1 against IL 1β, IL 6 and TNF-α was 7.5 mM, 28.65 mM and 45.87 mM respectively. Conclusion: Our data demonstrated thatthe TRP 1 treatment improved clinical score in acetic acid induced colitis in rats. It also inhibited the proinflammatory cytokine IL-6, IL 1β and TNF α and improvements of antioxidant in colitis rats through A2B receptor antagonist property.