This experiment was aimed to determine the significance of dose by comparing acute oral toxicological potential of nano-sized zinc oxide (20 nm) with its micro-sized zinc oxide. Sprague Dawley rats, 8 to 9 weeks old, were administered with 5, 50, 300, 1000 and 2000 mg/kg body weight (b.w.) of nano- and micro-sized zinc oxide suspended in distilled water once through oral gavage. The effects of the micro- and nano-sized zinc oxide on biochemical and hematological parameters were analyzed on day 14 of administration. The organs were collected for histopathology. Interestingly, inverse dose-dependent increase was noted in aspartate aminotransferase, alanine aminotransferase serum levels of nano-size zinc oxide groups when compared with their micro-sized zinc oxide. Clotting time was effected in all the male groups of nano-size zinc oxide, except in 1000 mg/kg b.w. The incidences of microscopic lesions in liver, pancreas, heart and stomach were higher in lower doses of nano-size zinc oxide compared to higher dose. However, the incidences of above lesions were higher in rats treated with a high dose of micro-sized zinc oxide. We conclude that nano-size zinc oxide exhibited toxicity at lower doses, thus alarming future nanotoxicology research needs to be focused on importance of dose metrics rather following the conventional methods while conducting in vivo experiments.