Zinc oxide nanoparticle is one of the most researched types of metal oxide nanoparticles in recent literature. Due to its unique properties such as biodegradability and reduced toxicity compared to other types of metallic nanoparticles, the application of zinc oxide nanoparticles has been increased in recent years. Most notable application is in the field of nanomedicine. Due to its ability to selectively kill cancer cells, zinc oxide nanoparticle has been used as a drug carrier for many chemotherapeutic drugs. The In vitro and in vivo models help us to understand the mechanism and the amount of toxicity induced by these nanoparticles in the immune system of humans. This can help in the formulation of personalized chemotherapeutic drugs. In this study, we analysed three differently synthesized zinc oxide nanoparticles (chemical precipitation, green chemistry approach, commercially available) on in vitro (human peripheral blood) and in vivo (Zebrafish) models. Pre-defined concentrations nanoparticles (5 µg/ml, 10 µg/ml, 15 µg/ml, 20 µg/ml, 25 µg/ml and 30 µg/ml) were used to analyse the amount of toxicity induced by zinc oxide nanoparticles. There was a dose dependent toxicity increase with in vitro and in vivo models after addition of zinc oxide nanoparticles. Commercially available zinc oxide nanoparticles showed highest toxicity and nanoparticles synthesized by green chemistry method showed lowest toxicity on comparison.