In the present work, we studied some qualitative and quantitative characteristics of mast cells located in the peritoneal cavity, submandibular and dorsal lymph nodes and ileum of Calomys callosus experimentally infected by Toxoplasma gondii. In uninfected animals, the majority of mast cells had similar ultra-structural characteristics, including several cytoplasmic granules with homogeneous and electron dense contents. However, after 1 h of infection, a significant influx of mast cells into peritoneal cavity was observed. The number of mast cells in this compartment decreased progressively in infected animals, and was significantly lower than the number of mast cells in control animals after 48 h of infection. Mast cells from infected animals or from purified suspensions that were infected in vitro presented significant morphological modifications, suggesting a degranulation process: cytoplasmic granules with electron dense content, fusion of the cytoplasmic granules, intracytoplasmic channels, cytoplasmic granules with flocculent material, plasma membrane rupture and granule contents in the extracellular environment. A remarkable increase in the influx of neutrophils toward the peritoneal cavity of the infected animals was observed after 12 h of infection. Moreover, this event occurred after the mast cell degranulation process took place. The relative increase in the number of mast cells and neutrophils was also followed by an increase in the number of macrophages, but there was a significant decrease in lymphocyte influx. After 48 h of infection, the parasite had spread from the peritoneal cavity to all organs examined. Also, mast cells from these organs showed evident morphological alterations, indicating the presence of the degranulation process. These results suggest that mast cells are deeply involved with the acute phase of the inflammatory response in this experimental model.