Nano-sized materials are increasingly used in cosmetics, diagnosis, imaging, and drug delivery. It also involved in specific functionality with lymphoid systems. However, the toxicity and mechanisms of quantum dots (QDs) uptake into mammalian cells are poorly understood. Our study was to investigate the toxicity and tissue uptake of polyethylene glycol-folic acid-conjugated (PEG-FA), and only polyethylene glycol-conjugated (PEG) cadmium selenide/cadmium sulfide (CdSe/CdS) QDs using precision-cut spleen slices of Sprague-Dawley (SD) rats. QDs were treated with different doses (0-300 nM) to the spleen of SD rats, and their toxic effects and tissue uptake were examined by LDH, NADPH oxidase, and histological analyses. No dose-dependent changes in LDH were observed. But high uptake of the QD-PEG-FA into spleen slices was observed by fluorescence microscopic examination in dose-dependent manner, while most of the QD-PEG was found on the edge of the slices. The NADPH oxidase activity was increased at high dose (300 nM) in both QD-PEG-FA- or QD-PEG-treated spleen slices indicating oxidative stresses. No damages were noticed in histological study confirming no toxicity in both types of QDs. Based on the above observations, we may conclude that surface coating property is an important factor in determining QDs uptake into mammalian cells. These findings provide insight into the specific mechanism of QDs uptake in cells.