Escherichia coli (E. coli) is considered one of the microorganisms that characterized as a double edge sord by their pathogenic role as well as commensal role. Lipopolysaccharides (LPS) is considered one of the endotoxins which are secreted by gram negative bacteria including E. coli Nanoparticles (NPs) are natural metals that have the ability to access through such a different micro spaces area in the body suggesting the drug delivery function of these NPs. In this current study, after uploading the LPS on the ZnO, The results of the current study suggesting the delivery role of zinc oxide giving the rise for LPS to access through more larger area surfaces in the body which leading to significant immune response of different parameters in the body  including  body temperature , pyrogenic activity , Antibody titration as well as the level of the proinflammatory cytokines (TNF α) compared to LPS alone. Taken together, our data indicated a significant role for the Nanoparticles particularly zinc oxide promoting the antigenic and pathogenic role of LPS compared to LPS alone, this may suggest the future role that these nanoparticles may be playing through delivering other natural compounds or drug in a consistent doses which may increasing the role of NPs in the field of drug delivery and drug safety which leading to   improve  the outcome of the treatment.