The etiology of intussusception (IN) remains largely obscure. In lipopolysaccharide (LPS)-induced IN, an experimental model in mice, IN is considered to be the consequence of altered intestinal motility as a result of increased nitric oxide (NO) along various inflammatory mediators. These could be decreased via cyclooxygenase (COX) inhibition by indomethacin. N-omega-nitro-L-arginine methyl ester (L-NAME) inhibits nitric oxide synthase (NOS) and NO production. Indomethacin is known to prevent IN; however, the reason is unknown. In this study we aimed to determine the role of NO, the effects of inhibition of its production by L-NAME and indomethacin, and whether preventive effects of indomethacin on LPS-induced IN were related to NO inhibition. A total of 113 mice were divided into seven groups. In the control group (n=6), no procedure was done. In the sham group (n=6), 1 ml saline was given; in the indomethacin group (n=6), 10 mg/kg of indomethacin was given; and in the LPS group (n=30), 12 mg/kg of LPS was administered intraperitoneally (IP). In the LPS+indomethacin group (n=32), 10 mg/kg of indomethacin was administered IP simultaneously with 12 mg/kg of LPS. In the L-NAME group (n=6), 20 mg/kg of L-NAME was administered subcutaneously. In LPS+L-NAME group (n=27), 20 mg/kg of L-NAME was administered subcutaneously with 12 mg/kg of LPS IP. All animals were laparotomized 6 h following injections. Existence of IN was noted and blood specimens were obtained. NO was quantified by measurements of nitrite and nitrate, obtaining a total of NO metabolites (NOx). The results were compared using the Mann-Whitney U-test and Spearman correlation test. A value of p<0.05 was considered significant. A total of 17 mice (one in control, 10 in LPS, four in LPS+indomethacin, and two in LPS+L-NAME groups) were excluded from the study because of death or insufficient blood collection. LPS (12 mg/kg, IP) induced IN at a rate of 30% (n=6) in the LPS group. Mean NOx levels were statistically higher in the LPS group (186.67+/-20.06) compared with other groups (p<0.05). Mean NOx levels were significantly higher in the group of mice with IN than in those without in the LPS group of this study (295.46+/-16.42, 140.05+/-15.44, respectively, p<0.05). The mean NOx levels were statistically lower in the LPS+L-NAME(23.94+/-3.39) group than the LPS+indomethacin (106.77+/-24.54) group, with no IN detected in neither of these two groups. Increased NOx levels induced by LPS correlated well with the occurrence of IN, and decreasing these levels via COX inhibition by indomethacin or NOS inhibition by L-NAME totally prevented IN from forming in this study. By these observations, it could be concluded that NO is probably involved in the pathophysiology of IN in this experimental model of LPS-induced IN.