Abstract: The pathological changes present in tilapia(Oreochromis niloticus)naturally infected by Streptococcus iniae were described under optical and transmission electron microscope.Gram positive and sphere-shaped bacteria were isolated from the liver,spleen,kidney and brain.The diameter of the sphere-shaped bacteria was approximately 0.6-1.0 μm.Most were arranged in chains.Histopathological examination showed edema,hemorrhage,degeneration,necrosis and the inflammatory response in many organs,especially in liver,spleen,kidney and brain.Further,hepatitis,splenitis,interstitial nephritis,and meningitis with numerous lymphocytes or macrophages infiltrates were evident.Ultrastructural pathology examination confirmed extensive systemic infection.Cytopathological changes showed that ultrastructure damages in visceral organ cells.Cells containing aberrant nuclei appeared singly or in clusters,which seemed to be apoptotic(morphologically became pyknotic,karorrhexis and karyolysis).The main alterations concerned the endoplasmic reticulum and the mitochondria:a high development of both rough and smooth endoplasmic reticulum(RER and SER),degranulation of RER,dilatation and vesiculation of reticulum cisternae were common.The mitochondria were swelling,with disappearance of cristae and vacuolization.These observations indicated that S.iniae could cause simultaneous development of multiple-organ lesions with an acute systemic inflammation in the host,and the fish were dead in the end.