Acute rejection (AR) remains a concern for kidney transplantation. Cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. Single nucleotide polymorphisms (SNPs) in cytokines and their receptors may relate to AR. We investigated the relation between AR and SNPs in the genes encoding for IL-2(–330G>T), IL-10(−592C>A and −1082G>A), TGF-β1(915G>C), and IL-2RB(rs228942 C>A and rs228953 C>T) in 325 renal transplant patients during the first year after transplantation. The overall incidence of AR was 15.4%. In multivariate analysis, only the use of induction therapy was correlated with AR (odds ratio 1.9; 95% confidence interval 1.1–3.7; p = 0.04). No statistically significant associations between the SNPs studied and AR were observed. SNPs in the investigated cytokines and their receptors were not associated with the risk of AR. Genotyping patients for these SNPs is unlikely to aid the clinician in adjusting the immunosuppressive therapy for individual patients.