Clarithromycin is an antibiotic widely used for Helicobacter pylori (H. pylori) eradication and together with amoxicillin and proton pump inhibitors they constitute the first line triple treatment regimen against H. pylori. Diarrhoea is one of the major drawbacks during H. pylori eradication and is majorly attributed to clarithromycin, while Saccharomyces boulardii is a probiotic and is shown to be effective in the treatment of antibiotic associated diarrhoea. We aimed to evaluate the effect of clarithromycin on orocecal transit in rats and to identify whether the supplementation with S. boulardii has a role on orocecal transit index. Adult rats of both sexes were divided into two groups to determine immediate or chronic effects of S. boulardii and clarithromycin on orocecal transit. The first group was given single dose of the test drug, while the second group received the test drugs for one week through orogastric intubation. Both groups were randomly distributed into four subgroups; the placebo group (group A), the S. boulardii group (group B), the clarithromycin group (group C), and the co-administration that is clarithromycin plus S. boulardii group (group D). Rats were given 20 mg kg(-1) clarithromycin and 500 mg kg(-1) S. boulardii. We did not find any difference among the subgroups in group 1, where only single dose of the test drugs was administered. In chronic administration group, that is group 2, significant differences among the subgroups were observed (P=0.004). Post-hoc comparisons of orocecal transit index between group "2A and 2C" and "2C and 2D" were significantly different (P=0.013 and P=0.005, respectively). Our results show that long term clarithromycin administration leads to rapid orocecal transit index and S. boulardii supplementation to clarithromycin can abolish this adverse effect in rats. Those findings suggest the beneficial use of S. boulardii in H. pylori eradication regimens.