Abstract: Using the method of “random sampling in typical colonies of the central area of the habitat ” and several electrophoresis techniques, the variations of 16 structural loci encoding blood proteins in Smalltailed Han sheep and Tan sheep were examined and compared with those of three other sheep populationsMongol sheep, Hu sheep and Tong sheep to explore their genetic differentiation. The coefficients of genetic differentiation at the structural loci were all below 7.341 7% except for Alp and X-p loci. The differences among populations were less than 5.370 5%. The standard genetic distance and fuzzy clustering showed the phylogenetic relationships among Mongol sheep and each of Hu sheep, Tong sheep, Small-tailed Han sheep and Tan sheep gradually estranged. Whether genetic approach degree was fit to compare the relationships among the analyzed populations and their known founder′s modern population or not needed further verification. This study further affirmed Small-tailed Han sheep and Tan sheep had the properties of Mongol sheep and revealed partial genetic differences of five sheep populations based on the structural loci.