Bartonella henselae is an agent capable of causing a wide variety of disease syndromes and is an emerging pathogen that causes potentially fetal opportunistic infection in patients with acquired immunodeficiency syndrome. The most common B. henselae-associated diseases are cat-scratch disease and bacillary angiomatosis. In this study, the interaction between B. henselae strains and endothelial cells was studied and the candidates in response to the pathogenesis were also determined. We identified that B. henselae infection inhibited the mitochondria intrinsic pathway and the strain stimulated more cell proliferation would suppress more intrinsic apoptotic pathway. Houston-1 (Hous) strain possessed the strongest ability in stimulating cell proliferation and inhibiting infection-induced apoptosis. Further more, Hous, U-4 and JK40 induced more ROS production than JK47 did. In bacterial adhesion abilities, genotype II (U-4 and JK40 strains) showed better adhesion abilities than genotype I (Hous and JK47). However, the invasion ability of Hous was the best among all the strains. Hous and JK47 (genotype I) could also induce more IL-8 (proinflammatory factor) production than U-4 and JK40 (genotype II) did. In proteomic analysis, two-dimensional gel electrophoresis and real-time PCR analysis were used to identify virulence factors in B. henselae. The mRNA levels of small heat shock protein, succinyl-CoA synthetase subunit beta, phage related protein and superoxide dismutase [Cu-Zn] precursor were increased in B. henselae after infection. These proteins might play important roles in pathogenesis of B. henselae.