Objective To explore the association between genetic polymorphisms and haplotypes of tumor necrosis factor-related apoptosis inducing ligand (Trail) and ulcerative colitis (UC).Methods A total of 331 patients with UC and 832 age and sex-matched healthy controls were collected.After Trail gene was amplified by PCR,the genetic polymorphisms of three single nucleotides (G1525A/G1588A/C1595T) in 3' non coding regions of Trail gene were examined by direct sequencing.The relation between Trail haplotype and UC was analyzed.Results Compared with control group,the frequencies of variant allele A and genotype GA+ AA in Trail G1525A were significantly lower in UC group (both P＜0.01).The frequencies of variant allele A and T in Trail G1588A and C1595T were also significantly lower in UC group than that of control group,and the difference was statistically significant (both P ＜ 0.01 ).In mild and moderate UC patients,the frequencies of variant allele T and CT+TT in Trail C1595T were 49.15％ and 64.51％,in severe UC patients were 72.37％ and 84.21％,and the differences were significant between the two groups (OR=2.710 and 2.935,95％CI:1.598～4.596 and 1.188～7.249,all P ＜0.05).In severe UC patients,the frequency of variant allele A in Trail G1525A was 48.69％,which was higher than that of mild and moderate patients (35.16％,OR=1.750,95％CI:1.082～2.830,P=0.021).In UC group,the frequency of AAT haplotype was significantly lower than that of controls (43.09％ vs 58.41％,P＜0.01).The frequency of GAT haplotype was significantly higher in UC group (10.15％vs 0.18％,95％ CI:0.005 ～ 0.051,P＜ 0.01).Conclusion The genetic polymorphisms and haplotypes of Trail (G1525A/G1588A/C1595T) gene may be closely correlated with the susceptibility to UC.