The aim of this study was to determine the relationship between EGC degranulation in fish injected with formalin-killed Escherichia coli and the effect of dexamethasone, diphenhydramine supplied separately and before formalin-killed E. coli. We performed a quantitative analysis of the number of cell granules and demonstrated that: compared to the EGCs of animals, the injection of dead E. coli with formalin generated degranulation of the EGC, while the administration of dexamethasone alone did not show significant differences with control group animals. The administration of diphenhydramine alone did not show significant differences neither with the animals of the dexamethasone treated group nor with those of the control group. When dexamethasone was administered one hour before the E. coli injection, degranulation was apparently inhibited and the number of granules did not show significant differences either with the animals in the control group or with those treated with dexamethasone. Finally, when this group was compared with the group of animals that were only injected with E. coli, the differences were statistically significant. However, when diphenhydramine was administered one hour before E. coli injection, a critical inhibition of EGC degranulation was evidenced, with a marked increase in the number of granules. All this seems to show that dexamethasone can partially inhibit the release of substances that participate in the inflammatory process. Diphenhydramine, a recognized antihistamine, inhibited degranulation of EGCs. These results suggest that EGC can release histamine like mammalian mast cells.