The aims of this study were to investigate the relationship of the genetic polymorphisms of serotonin reuptake transporter (SERT) to the clinical subtypes of irritable bowel syndrome (IBS), and the influence of the genetic polymorphisms on the efficacy of tegaserod in the Chinese patients with constipation IBS (C-IBS). The genetic polymorphisms were analyzed in 87 IBS patients and 96 controls, then 41 C-IBS patients were received tegaserod for a 4 weeks treatment. Primary efficacy variable was the responder rate measured with Subject’s Global Assessment of Relief. Secondary efficacy assessed the changes of individual symptoms weekly. There was no significant difference of genotype frequencies between the whole IBS and control group. However the frequency of L/L genotype in the 5-HT transporter gene linked polymorphic region was significantly higher in the C-IBS subgroup than in control group (25.0% vs. 7.3%). The responder rates of tegaserod in S/S (85.0%) and L/S (70.0%) were significantly higher than in L/L genotype (36.4%). All secondary variables were also significantly improved in S/S and L/S group compared to L/L group. This small sample size study suggested a hypothesis that people with L/L genotype were vulnerable for development of C-IBS, and C-IBS patients with L/L genotype responded poorly to routine dosage of tegaserod treatment.