The thoracic cavities receive increasing attention in toxicology, because inhaled fibers and (nano)particles can reach these cavities and challenge the local lymphoid tissues. The thoracic and abdominopelvic cavities are controlled by the serosal immune system with its special, loosely organized lymphoid clusters, namely the fat-associated lymphoid clusters and milky spots, which together can be denoted as serosa-associated lymphoid clusters. These clusters house numerous innate lymphoid cells, namely the nonconventional, innate B lymphoid cell and innate lymphocyte type 2 populations. The fat depots in the thorax play a significant role in the serosal immunity, and they can be modulated by health issues such as metabolic syndrome. The serosal immune system operates in a unique way at the interface of the innate and acquired immunity and therefore exposure-related modulation of the system may have a distinct impact on the body's immunity. To add to the investigation of the serosal immune system in the thorax, this review describes the (micro)anatomy of the immune system in relation to exposure, with a focus on the rat and mouse as preferred species in toxicology and immunology.