The liver of fish is considered an ideal model for studying the collaboration between environmental agents and the
health state of the fish, where it gives good indications about aquatic ecosystem status. Therefore, this study presented
immune roles for the liver in molly fish (Poecilia sphenops), using immunohistochemistry and transmission
electron microscopy (TEM). The hepatocytes’ sinusoidal structures of molly fish livers had taken two different forms;
cord-like and tubular, while the biliary tract system showed two different types: isolated and biliary venous tract. The
TEM showed that the hepatocytes possessed well-developed cytoplasmic organelles and numerous glycogen and
lipid droplets of different sizes. Kupffer cells, Ito cells, aggregation of intrahepatic macrophages and melanomacrophages
were also recognized. Melanomacrophages contained numerous phagosomes, many lysosomes, cytoplasmic
vacuoles, and melanin pigments. Hepatocytes and Kupffer cells expressed immunoreactivity to APG5, indicating
that these cells were involved in the process of autophagy. Telocytes (TCs) were also recognized in the liver of molly
fish, and they shared the same morphological characteristics as those in mammals. However, TCs expressed strong
immunoreactivity to APG5, TGF-β, and Nrf2, suggesting their possible role in cellular differentiation and regeneration,
in addition to phagocytosis and autophagy. Both IL-1β and NF-KB showed immunoreactivity in the hepatocytes and
in inflammatory cells (including intrahepatic macrophages and melanomacrophage center). Nrf2 and SOX9 showed
immunoreactivity in hepatocytes, stem cells, and macrophages. The present study showed the spatial distribution of
hepatic vascular-biliary tracts in molly fish. The liver of molly fish has unique functions in phagocytosis, autophagy,
and cell regeneration. The expression of APG5 in hepatocytes, Kupffer cells, melanomacrophages, and telocytes supports
the role of the liver in lymphocyte development and proliferation. The expression of TGF-β and NF-κB in hepatocytes,
Kupffer cells, telocytes, and macrophages suggests the role of the liver in regulation of cell proliferation and
immune response suppression. The expression of IL-1β and Sox9 in macrophages and melanomacrophages suggests
the role of the liver in regulation of both innate and adaptive immunity, cell proliferation and apoptosis, in addition to
stem cell maintenance.