In aquaculture today, vaccination of farmed fish is successfully providing protection against many of the most common pathogens. However, while vaccines are most commonly given as a single injection, this is not the ideal way of administration, as it is stressful for the fish and labour intensive and costly. A more desirable way of administration is by the oral route, where vaccine-formulations can be incorporated into the fish feed and given repeatedly. Encapsulation strategies such as nanoparticles, that protect antigens and give a long and sustained release, have shown to be a promising strategy for oral vaccinations. However, little is known about the mechanisms involved in uptake and trans-epithelial transport of particles in the nano/micrometre range in the fish intestinal system. To date, there are only a few studies addressing the effect of different characteristics of particles on uptake, transport and immune stimulation capability in fish. Here we report an adult zebrafish model system to study the uptake of different types of particles in the fish intestine and their interactions with epithelial cells and the mucosal immune system. We have used a protocol for oral intubation, which enables us to deliver fluorescent particles and bacteria directly into the adult zebrafish intestine. By histochemical methods and confocal laser microscopy, we are able to follow the uptake, transport and distribution of particles in the intestine and other organs over time. In a second line of experiments, we studied the ability of a well-known bacterial fish pathogen (M. marinum) to infect via the gastro-intestinal system in our model system. Oral intubation of adult zebrafish is therefore a powerful model system to study both the uptake and transport of particles via the gastro-intestinal tract and the interaction of pathogenic bacteria with the fish intestinal epithelia.