Objective：Our study aims to investigate the correlations between single nucleotide polymorphism rs2392221 in vascular cell adhesion molecule 1（VCAM1） and the risk of acute rejection（AR） in renal transplant recipients. Methods：A total of 200 Chinese renal transplant recipients who underwent kidney transplantation at our center of the First Affiliated Hospital of Nanjing Medical University， were enrolled and divided into non-AR group（n=131） and AR group（n=69）. The VCAM1 rs2392221 genotypes were detected by next generation sequencing. Five adjusted inheritance models were utilized to investigate the influence of VCAM1 rs2392221 on AR. Combining clinical and demographic data，the association between VCAM1 rs2392221 gene polymorphisms and AR in renal transplant recipients was evaluated. Results：The SNP rs2392221 on VCAM1 gene exhibited significant correlation with the occurrence of AR in four of the five models as P < 0.001 in codominant model（CC vs. CT：OR=3.71，95%CI：1.82~7.58；CC vs. TT：OR=5.41，95%CI：1.14~25.75），P < 0.001 in dominant model（OR=3.90，95% CI：1.97~7.72），P=0.357 in recessive model（OR=3.57，95% CI：0.77~16.54），P=0.002 in over-dominant model（OR=3.31，95% CI：1.65~6.65），P=0.034 in log-additive model（OR=3.04，95% CI：1.70~5.43）. Conclusion：In this study，we observed that SNP rs2392221 was significantly related to the occurrence of AR in Chinese renal transplant recipients，thereby indicating a potential target for the early diagnosis of AR.