Nile tilapia belongs to the family Cyprinidae. All fishes are at risk of pathogenic and other microbes, because fishes are contain by environment which is rich in microorganisms. Fish exist in environment of water which is useful because mucus is produce from the body of fish and protect against the large number of microbes which are present in the water. Usually the body of fish is protected by the layer of mucus and the mucus contain many kinds of biological constituent in the outer layer, these are the mucus cells, the club cells and the epithelial cells. The fish immune system is very important. The fish mucus having several unwilling defiance parameter which are immunoglobulin’s, pathogen peptide and harmonize factors that provide both physical and machinal protection. Important part of the fish mucous defense system is immunological defense that is present in mucus of fish’s skin, helping as a physiological and structural barrier against outside risks. Genetic makeup and evolutionary lineage determine the innate immune system of pathogens that are modified through time, pathogenic association and environmental factors.