Recent studies suggest that high pre and post renal transplant soluble CD30 (sCD30) levels may be associated with increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of serum sCD30 for prediction of acute graft rejection. In this prospective study, we analyzed clinical data of 40 patients, whose pre and post transplant (on day 14) serum levels of sCD30 were detected by ELISA. Eight patients (20%) developed acute rejection (AR),12 patients showed delayed graft function (DGF) and 20 recipients experienced uncomplicated course group (UC) respectively. The patients were followed for 3 months. Preoperative sCD30 levels of three groups were 96.2 ± 32.5, 80.2 ± 28.3 and 76.8 ± 29.8 U/ml, respectively (p = 0.28). After transplantation significant decrease of sCD30 was detected in three groups on day 14 post-transplantation respectively (81.6 ± 30.4, 63.2 ± 28.5 and 55.5 ± 27.7 U/ml respectively, p<0.001), while sCD30 levels of AR group remained significantly higher than DGF and non-rejecting patients (24.3 ± 5.2, 18.1 ± 3.2 and 19.8 ± 4.7 U/ml respectively, p=0.02). Positive Panel reactive antibody (PRA) was not statistically different among groups (p=no significant).Also hemodialysis did not affect sCD30 levels (p=no significant). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 14 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 15 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). In conclusion, measurement of soluble CD30 on day 14 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.