The biodistribution and clearance in mice of near-infrared (NIR) ultra-small Ag2Se quantum dots (QDs) were systematically studied. The ICP-MS quantitative assessment and biodistribution fluorescent images of Ag2Se QDs in mouse organs demonstrated that the Ag2Se QDs could be cleared quickly from the mice body mostly by renal excretion without significant long-term organs accumulation. Pathological analysis, blood biochemical analysis, and body weight results also showed that the Ag2Se QDs do not cause appreciable toxicity in vivo.