Abstract Benefiting from low scatter of NIR-II light in biological tissues and high spatial resolution of confocal microscopy, NIR-II fluorescence confocal microscopy has been developed recently and achieve deep imaging in vivo. However, independence of excitation point and detection point makes this system difficult to be adjusted. New, improved, self-confocal NIR-II fluorescence confocal systems are created in this work. Based on a shared pinhole for excitation light and fluorescence, the system is easy and controlled to be adjusted. The fiber-pinhole confocal system is constructed for cerebrovascular and hepatocellular NIR-II fluorescence intensity imaging. The air-pinhole confocal system is constructed for cerebrovascular NIR-II fluorescence intensity imaging, hepatic NIR-II fluorescence lifetime imaging, and hepatic multiphoton imaging.