BACKGROUND/AIMS Gallbladder emptying abnormalities are common in patients with diabetes mellitus, and it has been hypothesized that they contribute to the increased incidence of gallbladder stones and biliary pain observed in these patients. Cisapride is a drug that exerts a prokinetic effect in both animals and humans. Recently, we demonstrated that cisapride decreased the fasting and post-prandial gallbladder volume in healthy subjects. Therefore, we investigated the action of cisapride on gallbladder contraction in diabetic patients. METHODOLOGY Twenty diabetes mellitus patients and 20 healthy volunteers participated in this study. On the day of the study, ultrasonography was performed at 9 am, after 12 hours of fasting. After the basal measurement was obtained, the diabetic patients and healthy subjects received 10 mg cisapride or a placebo peroral. Two hours later, gallbladder volumes were rescanned by ultrasonography at 15-minute intervals for 60 minutes. RESULTS The fasting gallbladder volume was 19.8 +/- 6.7 ml in the diabetic patients, and after the administration of cisapride, the gallbladder volume decreased by 32.2%-38.6% as compared to the baseline (p<0.02, 0.05, 0.01) and by 35.0%-45.8% as compared to the diabetic controls (p<0.02, 0.05, 0.001). In the healthy subjects, cisapride did not change the fasting mean gallbladder volume as compared to the baseline. After the administration of cisapride in the diabetic patients, the mean gallbladder volume decreased more than in the healthy subjects. The mean gallbladder volumes of the diabetic patients were between 12.1 +/- 4.2-13.4 +/- 4.2 ml. In the healthy volunteers, after the administration of cisapride, the volume was reduced by 1.9%-11.3% as compared to the healthy control group, but the volume changes of these two groups were not statistically significant. CONCLUSION This study shows that the administration of cisapride causes gallbladder volume reduction in diabetic patients.