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Objective: To find out the relationship of ecological environment protection and the transmission of Lyme disease under economic development of western regions in China., Methods: Both scene molecular and traditional epidemiological methods were used to assess the effects of environmental protection on the transmission of Lyme disease., Results: Among areas as protected natural forests, semi-protected nursery forests and farmland, the vector tick species and reservoir rodents from protected natural forests area had the highest quantity of population and diversity index and followed by semi-protected nursery forests. Vector competence of reservoir hosts and value of natural foci from protected natural forests area were also remarkably higher than those areas of semi-protected nursery forests and farmland. Staff working in the areas who were bitten by ticks from protected natural forests areas had higher serological positive rate (66.7%) than those from semi-protected nursery forests areas (2.5%), and both showed remarkable difference (P = 6.45, E-11 < 0.01, df = 1). The difference of genetic divergence among these subpopulations from different habitats being surveyed showed that the biggest genetic divergence index (F(st)) of 0.557 42 was between protected natural forests area and farmland area. The index between semi-protected nursery forests area and farmland area was also bigger than zero with statistical significance. The genetic divergence index of 0.108 02 between semi-protected nursery forests area and protected natural forests area was the lowest which showed that genetic divergence between the subpopulations of the two sampling areas was not obvious. The genetic distance among these subpopulations had similar change along with their habitats., Conclusion: Under economic development of western regions in China, when programs as natural forests protections, recovery prairie and grassland from farmland were actively performed, vectors insects and reservoir hosts of Lyme disease might also be protected to some degree but the risk and value of natural foci on Lyme disease might increase. Data suggested that people entering these areas should be told to strengthen their awareness on individual protection against the disease.