Cancer is one the most concerning complication of longstanding ulcerative colitis [UC] . This study was undertaken to investigate the possible association between eNOS gene intron 4 polymorphism and the development of UC-associated colorectal cancer. It was carried out on 120 subjects; distributed as follows: 40 patients with UC associated colorectal cancer, 40 patients with UC who did not develop colorectal cancer and 40 control subjects. Genotypes [aa, bb, ab] for eNOS gene intron 4 polymorphism were identified using amplified fragment length polymorphism PCR. Plasma nitrate and nitrite levels were used to estimate the amounts of endogenous nitric oxide formation using nitric oxide colorimetric assay kit. Our preliminary data revealed that, compared to the bb genotype, the aa and ab eNOS genotypes were significantly associated with increased risk of developing UC associated colorectal cancer. Meanwhile, in UC associated – colorectal cancer and UC patients groups, plasma NO levels were higher in patients with 4a4a/4a4b genotypes compared to those with bb genotype. It can be concluded from our preliminary study that a allele variant of eNOS intron 4 polymorphism may be associated with increased risk of development of UC associated colorectal cancer, however, large scaled studies are needed to verify these preliminary results