Background: FOXP3 gene, is a major regulator of T-regulatory (Treg) cells that have a critical role in immune responses to alloantigens and acute cellular rejection (ACR) after liver transplantation (LT). Objectives: To investigate the role of FOXP-3 rs3761548 gene polymorphism on ACR after LT and to determine the relation between the circulating CD4+CD25+FOXP-3+Treg cells, and infection on the severity of ACR. Methodology: Blood samples were obtained from 60 allograft liver recipients and 20 healthy volunteers. FOXP-3 (rs3761548) polymorphism was studied using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Flowcytometry was used to enumerate circulating CD4+CD25+FOXP-3+Treg cells in peripheral blood of liver transplant recipients. Results: Bacterial and candida infections were more significantly detected in liver transplant recipients with ACR. A significant predominance of the AA genotype and the A allele of FOXP3 gene (rs3761548) was found in liver transplant recipients with compared to those without ACR. Highly significant reduction in percentage and count of CD4+and Treg cells were demonstrated in the liver transplant recipients with ACR. A significant negative correlation was detected between degree of ACR and percentage and count of Treg cells. Conclusion: Genetic polymorphism of FOXP-3 (rs3761548) and decreased percentage and count of Treg cells were associated with ACR. Carriers of the AA genotype and the A allele were more liable to severe degree of ACR after LT.