In the present study, an experimental infection with Streptococcus iniae was conducted with tilapia (Oreochromis niloticus). The bacterial agent was injected to the fish by intraperitoneal inoculation at a dose of 1 x 10(3) cfu / mL. Grossly, haemorrhages on tail and pectoral fins, hyperaemic and prolapsed anus, darkening and bleeding in the gills and exophthalmos in the eyes were identified in fish. Multifocal whitish foci in the liver, spleen and kidneys was observed with ascites. Histopathological changes of tissues of tilapia were studied and evaluated. Gill tissues of infected fish showed intense lymphocyte and macrophage infiltrations. In addition, epithelial cell separation and lamellar fusion with edema, lamellar curling and aneurysms were detected in gill tissue. Sinusoidal dilatation, lymphocyte infiltrations, congestion and degeneration in liver hepatocyte cells have been identified. In kidney degeneration of glomerulus and tubule cells and dense lymphocyte infiltrations were observed. Dense bacterial clusters were observed in the sinusoids of the spleen, while lymphocytes and macrophage infiltrations were found in the heart and intestinal tissues.