Zinc nanoparticles showed a great potential as mineral feed supplements in animals than the conventional sources. However, this potential has not been applied in rabbit nutrition. Therefore, this study was designed to evaluate the effects of dietary nano-zinc oxide on the growth performance, serum biochemical, economic parameters and gene expression of interleukin-6 in growing rabbits. A total of 120 male, five-week-old New Zealand White (NZW) rabbits were randomly distributed into four equal groups. The control group (Z0) was fed on a basal diet with zinc free premix; the other three experimental groups received the basal diet supplemented with 60 mg zinc oxide/kg diet (Z1), 60 mg nano-zinc oxide/kg diet (Z2) and 30 mg nano-zinc oxide/kg diet (Z3), respectively. The results revealed that rabbits in the groups Z2 and Z3 had higher body weight, daily weight gain, daily feed intake, serum total protein, globulin, IgG and SOD when compared with those of groups Z0 and Z1 (P<0.001). In addition, growth hormone level was higher in Z3 group than in the other groups, whereas no significant differences were recorded among the treated groups in respect to serum TSH concentration (P>0.05). Hepatic and serum zinc contents were high in Z2 and Z3 groups, but the copper contents were decreased. Rabbits of group Z3 yielded the highest gross margin with the lowest expenses to produce 1 kg of live weight compared with the others. The production of IL6 in spleen was increased in Z3 group than that in the other groups. Thus, it can be concluded that nano-zinc oxide at a concentration of 30 mg/kg diet may be used instead of the traditional zinc sources in rabbit diets.