BACKGROUND Osteopontin (OPN) is a potent proinflammatory cytokine that is upregulated in cell-mediated immunity and various inflammatory states of the kidney. However, the relationship between OPN levels plasma/urine and acute renal allograft rejection is still unknown. Therefore, we assessed the relationship between OPN levels in plasma/urine and acute cellular rejection post-renal transplantation. METHODS Clinical data and biologic samples of renal transplant recipients were analyzed retrospectively. Patients with biopsy-proved acute cellular rejection (ACR) (n = 22), protocol biopsy-proved non-rejection (non-R) (n = 16), and living related donors as healthy control (HC) (n = 10) were involved in this study. OPN level in plasma and urine was detected using the human OPN enzyme-linked immunosorbent assay kit. Type and grade of ACR were diagnosed based on Banff' 03 classification criteria of renal allograft pathology. No prisoners or organs from prisoners were used in this study. RESULTS Compared with non-R patients and HC, plasma and urine OPN levels in ACR patients were significantly increased (P < 0.05), whereas there was no significant difference between non-R patients and HC (P > 0.05). In ACR patients, plasma OPN level was positively correlated with Banff grading of acute rejection, and a cut-off value of 24.20 ng/mL was further demonstrated a good clinical value in receiver operation characteristic curve. CONCLUSIONS The data obtained suggested that assessment of OPN levels in plasma and urine, especially in plasma, should be useful in predicting and evaluating the severity of ACR in renal transplant recipients.