Platelets are the cellular mediator of thrombosis, but it is becoming increasingly evident that platelets actively participate in inflammation and immune responses. A recent paper indicated that platelet factor 4 (PF4) alleviated cardiac allograft rejection in mice. But the role of PF4 on kidney transplantation has never been investigated. In our current experiment, PF4 administration alleviates immune responses to kidney transplantation. PF4 significantly alleviates vascular and glomerular changes, as well as interstitial inflammation, fibrosis, and tubular atrophy at day 56 after transplantation. PF4 decreases interleukin (IL)-17 production in vivo and also limits Th17 differentiation in vitro. Furthermore, the alleviated chronic vasculopathy and tubulointerstitial inflammation induced by PF4 were abolished with additional IL-17 administration. Meanwhile, decreased serum creatinine and urea induced by PF4 were also reversed by recombinant mouse IL-17 (rmIL-17). In conclusion, PF4 plays a protective role in chronic kidney allograft and this was associated with inhibition of IL-17 production.