Background Acute kidney injury is a serious complication of morbidity and mortality with critically ill patients in short and long-term. Severe trauma patients especially followed infection will induce acute kidney injury. Methods C57BL and C57BL background CD200 deficiency mice were applied to undergoing the operation of cecal ligation and puncture following hemorrhage. The model was used to simulate the process of shock patients followed infection, which associated with acute kidney injury clinically. Blood and kidney tissues were harvested 24 h after hemorrhage/cecal ligation and puncture. CD200 expression on neutrophils and monocytes in blood was stained and measured via flow cytometry analysis. Serum creatinine and blood urea nitrogen were measured according to the manufacturer’s instruction. Cytokines and counterpart RNA expression were detected via ELISA and RT-PCR, respectively. The severity of kidney injury was assessed by pathologists. The protein level of neutrophil gelatinase-associated lipocalin and high mobility group 1 was measured via western blot. Outcome CD200 expression was elevated on neutrophils and monocytes in blood. Furthermore, the severity of kidney injury of histology, assessed by pathologists, was much aggravated on acute kidney injury and even exacerbated on CD200 deficiency mice. The levels of serum creatinine and blood urea nitrogen were all increased in CD200 deficiency mice. Cytokines of IL-6 and TNF-α increased in acute kidney injury and even aggravated in CD200 deficiency mice, but IL-10 was demonstrated the reversed trend. The consistent trend of RNA expression of cytokines including IL-6, TNF-α and IL-10 was corroborated via RT-PCR. As western blot demonstrated, the protein level of neutrophil gelatinase-associated lipocalin was increased and high mobility group 1 decreased in CD200 deficiency mice. Conclusion CD200 may be involved in the development of hemorrhage/cecal ligation and puncture associated acute kidney injury. It may be speculated that CD200 plays a protective effect in acute kidney injury potentially through inhibiting neutrophil gelatinase-associated lipocalin and activating high mobility group 1 signaling pathway.