An aqueous chemical reaction has been used to prepare antifungal ZnS: Mn nanostructures, from manganese chloride, zinc acetate and thioacetamide in aqueous solution. The nanoparticle size has been controlled using thioglycolic acid as a capping factor. The major feature of the ZnS:Mn nanoparticles of average diameter ~ 2.73 nm is that possible preparing the sample from sources non-toxic precursors. The manufactured ZnS:Mn nanoparticles were identified and characterized to investigate the structure, morphology, composition of components of the nanoparticles and optical properties using (XRD, SEM, EDS and UV-Vis spectroscopy) techniques respectively. The agar dilution mechanism used to evaluate of the antifungal activity using ZnS:Mn nanoparticles which showed an efficient antifungal activity against four fungal models Aspergillus fumigatus ,Aspergillus falvus, Trichophyton mentagrophyte, and Microsporum audonii the inhibition increase with the increase of nanoparticle concentration. The antifungal property of manganese doped zinc sulphide nanoparticles creates from the interaction between nanoparticles and water led to generation the interactive oxygen species. Perturbation of the cell membranes due to the existence of Zn ions and S affecting on inhibition rate . the study aimed to evaluation the Antifungal Activity of ZnS:Mn Nanoparticles Against Some Isolated Pathogenic Fungi.