Monitor lizards are acclimatized to a variety of environments. Most of the monitor species are terrestrial, although there are arboreal and semiaquatic monitors. Such accommodation requires unique cellular structure and regulatory devices in various organs, particularly their lungs. This study aimed to report the pulmonary guardians and special regulatory devices that may guard and promote the function of the lungs of the Nile monitor lizards (Varanus niloticus). Specially structured vessels were recorded in the pulmonary tissue involving atypical glomus vessels, vessels with variable wall thickness, and a venule with specialized internal elastic membrane. Moreover, numerous lung resident guardians could be identified including both alveolar and interstitial macrophages, dendritic cells, mast cells, and B- and T-lymphocytes. Pericytes were demonstrated surrounding the capillary endothelium with a characteristic direct hetero-cellular junction with telocytes. Telocytes established a microenvironment through an indirect hetero-cellular junction with the interstitial macrophage, dendritic cells, and pneumocyte type II. Collectively, these data indicate a significant role played by the specially structured vessels and the resident immune cells in guarding the pulmonary tissue of the Nile monitor lizards and promoting its function. Telocytes are suggested to play a key role in angiogenesis and cellular communication to promote the function of the immune cells.