Helicobacter suis (H. suis) is the most prevalent gastric non-H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of non-human primates. Studies performed in rodent models suggest that differences exist in virulence between H. suis isolates obtained from pigs and monkeys, although most of these studies have used mucosal homogenate of H. suis-infected animals, due to the lack of in vitro cultures. The aim of this study was to obtain better insights into potential differences between pig- and primate-associated H. suis strains in virulence and pathogenesis. Therefore, in vitro isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis) and rhesus monkeys (Macaca mulatta) were used for experimental inoculation of BALB/c mice and Mongolian gerbils. Both porcine and rhesus monkey H. suis strains caused severe gastric inflammation in both rodent models. However, cynomolgus monkey-associated H. suis strain HsMf505/1 was unable to colonize the stomach of Mongolian gerbils. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig- and primate-associated H. suis strains evoked a marked Th17 response in mice and gerbils, accompanied by increased CXCL-13 expression levels. In conclusion, apart from cynomolgus monkey-associated strain HsMf505/1 which was not capable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence exist in rodent models between in vitro cultured pig-associated, cynomolgus monkey-associated and rhesus monkey-associated H. suis strains. Mainly the experimental host seems to determine the outcome of the immune response against H. suis infection, rather than the original host where strains are isolated from.