Ulcerative colitis (UC) is a chronic ulceroinflammatory condition primarily confined with in colonic mucosa with variable distortion of the colonic architecture. It is associated with microbial overgrowth such as E.coli , S. typhi .However Chloroquine acts on these microbes. In our present study the anticolitic effects of Chloroquine in treatment with the DSS induced model for UC in mice were examined. Male mice of age 7 weeks are chosen .They are assigned into different groups .Negative control groups treated with normal saline solution ,positive control group treated with DSS5%, standard group treated with Balsalazide 4mg/kg & DSS 5% , Test(1) group treated with Chloroquine 6mg/kg, Test(2) group treated with Chloroquine 8mg/kg, Test(3) group treated with Chloroquine 10 mg/kg then we performed different parameters such as DAI, Oxidative damage assessment, MPO Assessment and Histopathological evaluation. The results have showed that Chloroquine has significant activity against DSS(5%) induced colitis when compared to the experimental control, with near normalization of colon architecture. Tissue oxidative stress was reduced with significant improvement in tissue levels of MDA, GSH, SOD and CAT .Furthermore,significant improvement in levels of myeloperoxidase (MPO) was observed. It is concluded that Chloroquine(10mg/kg) has got potent activity against DSS(5%) induced ulcerative colitis(UC) due to its anti inflammatory antioxidant properties.