Activation of proteinase activated receptors (PARs) occurs in, and contributes to, the pathogenesis of rheumatoid arthritis (RA). Recently PARs have been proposed to act as a sensor system to detect infection. The increased infection and exposure to microbial products has been proposed as a trigger for RA onset in susceptible individuals. In this study, we investigated whether deficiency of PAR1 or PAR2 affects the onset and development of RA in a murine collagen-induced arthritis (CIA) model and the neutrophil bacterial killing ability in vitro. CIA was induced in PAR1 and PAR2 gene knockout (KO) and wild type (WT) mice. Neutrophils were isolated from mouse spleens and used to test their bacterial killing ability at the presence or absence of interferon (IFN)-γ. In the CIA model, arthritis incidence and severity in PAR1 and PAR2 KO mice were more than 50% higher (P<0.01) than that in WT mice three weeks after the second collagen immunization. Interestingly, arthritis onset was observed within 1 week in PAR1 KO mice, after 1 week in WT mice and after 2 weeks in PAR2 KO mice after the second collagen immunization. PAR1 and PA2 KO mice also displayed higher serum levels of interleukin (IL)-17 than that in WT mice, with no detectable IFN-γ in any mice. In vitro, WT spleen cells produced higher levels of IFN-γ (P<0.05) than PAR1 or PAR2 KO cells in control conditions or in response to lipopolysaccharide. WT neutrophils showed greater bacterial killing ability (P<0.05) that either PAR1 or PAR2 KO cells. IFN-γ stimulated WT and PAR1 KO, but not PAR2 KO neutrophil bacterial killing ability. Our results indicate that deficiency in PAR1 or PAR2 exacerbates CIA with disease onsets earlier in PAR1 KO and delayed in PAR2 KO when compared to WT mice, and reduced the neutrophil bacterial killing ability in vitro.