Zinc oxide nanoparticles (nZnO) are used in a various range, including ceramic manufacture, photocatalysis, UV filters, and the food industry. However, little is known about the effects of micro- and nano-particles during mouse embryo organogenesis. To determine whether ZnO affects size-dependent anomalies during embryonic organogenesis, mouse embryos were cultured for two days with 300 ug/ml micro ZnO (mZnO;80±25 μm) and nZnO (< 100 nm) and the developmental changes were then investigated. Quantity of Zn by inductively coupled plasma mass spectrometry analysis, and expression patterns of various antioxidant enzymes in the embryos were investigated. Embryos exposed to mZnO or nZnO exhibited severe retardation of growth and development. In embryos exposed to mZnO and nZnO, yolk sac diameter, crown-rump length, and head length were significantly diminished. The morphological parameters, including yolk sac circulation, allantois, flexion, heart, hindbrain, midbrain, forebrain, otic system, optic system, branchial bars, maxillary process, mandibular process, olfactory system, caudal neural tube, forelimb, hindlimb, and somites in mZnO and nZnO-treated groups were significantly decreased. Zn absorption of the nZnO-treated group was significantly higher than that of the mZnO-treated group. Significantly decreased levels of CuZn-SOD, Mn-SOD, cGPx, and PHGPx mRNA were observed in the ZnO-treated group. In addition, antioxidant enzyme mRNA expressions of the nZnO group were significantly diminished, less than those of the mZnO treated group. These findings indicate that 300 ug/ml ZnO showed abnormality and nZnO may have a more severe effect than mZnO in developing embryos.