¹Agricultural Research Center (ARC), Animal Health Research Institute (AHRI), Department of Biochemistry, Toxicology and Feed Deficiency, Postal code 12618, Dokki, Giza, EGYPT DOI : 10.9775/kvfd.2022.28922 Zinc nanoparticles have a positive effect in enhancing growth and improving immunity, so this work aimed to investigate the role of Nano-zinc oxide as an immune stimulant and treatment of zinc deficient lambs in comparison with zinc in ordinary size. Thirty lambs were used and divided into three groups, the 1st group (N=10) control healthy group, the 2nd group (N=10) lambs suffered from zinc deficiency and treated with Nano-zinc oxide (nZnO), the 3rd group (N=10) lambs suffered from zinc deficiency treated with zinc oxide (ZnO) ordinary size. Serum samples were collected at zero-day (0-day), 7th, and 15th days of experiment. The serum analysis results of the zinc-deficient groups at 0-days revealed hypozincaemia, hypovitaminosis A and E, hypoproteinemia, hypoalbuminemia, hypoglobulinemia, decreased antioxidant (SOD, TAC, CAT, GSH) and immunoglobulin (γ2, γ1, β2, β1), while increased MDA, α2, and α1 compared to control healthy group. Most of parameters revealed rapid recovery from the 7th day of experiment in the nZnO group rather than the ZnO group. Some parameters of SOD, total protein, globulin, γ2, γ1, α2, and α1 appeared on the 7th day of experiment of the nZnO group significantly increased compared to the control healthy group, which revealed an improvement in the immune response. In conclusion; nZnO induced rapid recovery, and improved both immunity and antioxidants than zinc oxide ordinary sized. Keywords : Nano-zinc oxide, Zinc oxide, Vitamins, Antioxidants, Protein, Electrophoresis