Major histocompatibility complex is a genetic region of the chromosome. It consists of a series of closely linked highly polymorphic loci that stimulate the body’s immune response by encoding a class of cell surface transmembrane protein that binds to T lymphocytes and presents endogenous and exogenous antigens to it. Based on the techniques of homology cloning and RACE-PCRα was cloned from Nile tilapia. In additionere also analyzed. The total length of MHC1α cDNA was 1 553 bpwhich the ORF (open reading frame) was 1 053 bp in length. Sequence analysis showed that the deduced protein sequence of MHC Іα included a leader peptide teleosts and mammals. Six different MHC Іα cDNA sequences were obtained from six individuals. six MHC Іα cDNA sequences. This indicates that MHC Іα cDNA has abundant polymorphism. qPCR detected the highest expression level of MHC Іα in spleen and heartskin and muscle. Different changes were found in the expressions of MHC Іα mRNA in the gill. The findings provide useful information for further investigation to select a disease resistant molecular marker of Nile tilapia using MHC I