Abstract: OBJECTIVE To evaluate the virulence and pathogenicity of Staphylococcus aureus with incomplete hemolytic phenotype (SIHP) by using models of rats with bloodstream infections. METHODS Totally 44 SPF grade KM female mice with 6 weeks of age were enrolled in the study and were respectively injected with normal saline, novel SIHP and Staphylococcus aureus with complete hemolytic phenotype (SCHP) via tail vein to establish the models of mice with bloodstream infections. The enrolled mice were divided into the negative control group with 4 mice, the novel SIHP group with 20 mice and the SCHP group with 20 mice. The body weight and food intake were monitored daily. The blood samples were collected after the infections for 1, 3, 5, and 7 days, the blood routine tests were instrumentally carried out, and the levels of serum interleukin (IL)- 1β, IL-6, IL-10 and TNF-α were detected by means of ELISA. The heart, liver, spleen, lungs, and kidneys were aseptically removed, the bacterial loads in tissue homogenates were determined, and the histopathological damage was assessed by hematoxylin-eosin (HE) staining. RESULTS The SIHP group exhibited more severe suppression of food intake and weight loss than the SCHP group (P＜ 0.05), the percentage of monocyte and platelet counts were higher, the serum IL-6 level reached the peak 2 days in advance, with the concentration higher, and the peak value was higher (all P＜0.05). The bacterial loads in the heart, liver, spleen and lungs of the SCHP group reached the peak on Day 3, while the bacterial loads in the liver and spleen of the novel SIHP group reached the pean on Day 1, and the bacterial loads in the heart and lungs delayed reaching the peak until Day 5. The histopathological damage indicated that the SIHP group had more severe organic damage, manifesting as myocardial fibrosis, extensive hepatic steatosis, edema and congestion, pulmonary necrosis, and renal tubular necrosis with inflammatory infiltration. CONCLUSION The novel SIHP shows greater pathogenicity in the rat models than dose the SCHP, presenting more severe early inflammatory reactions, distinct organ colonization kinetics and more severe tissue damage.