Toll-like receptor (TLR) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune responses. Our aim was to investigate the distribution of TLR4 and TLR2 gene polymorphisms among pediatric renal transplantation patients in relation to chronic allograft nephropathy (CAN). In addition to 115 healthy controls, we included 69 renal recipients, 19 of whom were identified as CAN by biopsy scored according to the Banff criteria. Polymorphisms at TLR4 Asp299Gly and/or Thr399Ile were present in 11.6% of renal transplant recipients. None of these subjects was identified in cosegregation with the Thr399Ile allele, whereas three had an isolated Asp299Gly and five had an isolated Thr399Ile. Neither renal recipients nor healthy controls were homozygous for both Asp299Gly and Thr399Ile polymorphisms. However, TLR4 Thr399Ile polymorphism and lie allele was greater among CAN (-) versus CAN (+) recipients (P > .05). The frequency of TLR2 mutant type Gin allele was significantly higher in recipients than among healthy controls (P < .0001). However, the Gln allele frequency was similar between CAN (+) and CAN (-) patients. The results of present study may be speculated to show TLR4 and TLR2 gene polymorphisms as protective factors from CAN development due to impaired immune responses.