Mirtazapine is a noradrenergic and specific serotonergic antidepressant. The aim of this study was to investigate the effects of mirtazapine on gastrointestinal motility in dogs, including solid gastric emptying, antral and small intestinal contractions, small intestinal and colonic transit. Methods: Six dogs were implanted with two cannulas located at the duodenum and the ascending colon; Another 6 dogs were implanted with gastric cannula 6cm proximal to the pylorus. Mirtazapine 45mg was administered orally 90 minutes before the study. Results: 1). Mirtazapine accelerated gastric emptying during the entire 3 hours in normal dogs (P < 0.04) and accelerated delayed gastric emptying induced by rectal distention (P < 0.04). 2). Mirtazapine restored impaired gastric tone and accommodation induced by rectal distention (P < 0.05) 3) No significant changes were noted in small intestinal contractions or transit with mirtazapine (P > 0.1). 4). Mirtazapine accelerated colonic transit at 2 and 4 hours but not 6 hours. The geometric center (GC) was increased from 1.9 ± 0.6 to 3.0 ± 0.5, 3.9 ± 0.5 to 4.7 ± 0.1 at 2 and 4 hours respectively (P = 0.04 vs. corresponding control). Conclusions: Mirtazapine improves gastric emptying in healthy dogs and normalizes rectal distention-induced delay in gastric emptying and accelerates colon but not small intestinal transit in healthy dogs. Clinical studies are warranted to assess the effects of mirtazapine on gastrointestinal motility and sensory functions in patients with functional GI diseases.