In order to present clues to find safer and more efficient ciliary neurotrophic factor(CNTF), computer molecular modeling system was used to gain the three-dimension structure of CNTFRα.Then through analysing the CNTF/CNTFRα crucial sites to its bioactivity combined with the homologous sequences comparison and CNTF molecular characters, two CNTF mutants were designed. The mutants' bioactivity were tested by the experiment of TF-1 proliferation. The two mutants' bioactivity reached 10⁶ U/mg level after expression and purification and the bioactivity of A is higher than that of B. The results proved primarily that the design was reasonable and provided premise and basement for CNTF's development and application.