Abstract: ObjectiveThe infection approach of Streptococcus agalactiae to GIFT tilapia and target organs were stu-died to provide reference for disease resistant breeding and development of S.agalactiaevaccine.MethodThe GIFT tila-pia was inoculated by S.agalactiae through intraperitoneal injection,gavage and soak,and samples of gill,spleen,liver and small gut were collected for pathomorphology observation.Immunohistochemical location was conducted using anti-S.agalactiae serum of rabbit to research the distribution regulations in each tissues under various inoculation approaches and the inoculated target organs.ResultThe three artificial inoculation methods could all lead to S.agalactiae inocula-tion of GIFT tilapia.In intraperitoneal injection and gavage inoculations,pathological changes occured after 2 h of inocu-lation,but in soak inoculation,pathological changes occured after 5 h,and the degree of pathological changes was less serious than the other two.Immunohistochemical localization results showed that,in intraperitoneal injection treatment, the order of pathogenic bacteria occured in GIFT tilapia was spleen→liver and gill→small gut;the order in gavage inocu-lation was small gut→gill and spleen→liver;and the order in soak inoculation was gill→spleen→liver and small gut.ConclusionIntraperitoneal injection,gavage and soak can all lead to S.agalactiae inoculation in GIFT tilapia.The sig-nal of pathogenic bacteria would appear first in spleen,gut and gill.Therefore,the effective measures to control the out-break of S.agalactiaedisease in GIFT tilapia under natural aquaculture conditions are preventing the aquaculture water and food from infection of S.agalactiae.