Gastrointestinal system is predominantly supplied by the serotonin. Serotonin has both central & peripheral actions. The SSRls increases the release of serotonin in the synapse by inhibiting the transporter, which results in excessive nausea & vomiting initially. We carried out this study to determine the effects of SSRIs on intestinal motility. Power lab (USA) was used for recording the contractions of ileal smooth muscle of rabbit. The percent responses of serotonin, fluoxetine, paroxetine and citalopram were 100, 15.48, 7.45, and 6.75 percent correspondingly indicating that serotonin has a greater impact on intestinal motility as compared to SSRIs. Failure of SSRIs (fluoxetine, paroxetine and citalopram) to augment the serotonergic transmission in vitro causes a decline in its qualitative response. Fluoxetine causes the minimal effect on intestinal activity amongst its fellow drug & therefore can be prescribed safely in patients of depression with abnormal motility