Abstract: Objective: To offer a series of efficient methods to physiological researchers in following the four principles of experimental de-sign (hereinafter referred to as four principles).Methods: We expounded the concrete way of following the four principles through giving an outline of the four principles, elaborating the common mistakes and cases in the applications of four principles in physiological research and in-troducing briefly how to follow the four principles in physiological research.Results: We should choose the appropriate randomization method according to the actual situation, usually stratified randomization was a good way. We should strive to set reasonable control group to reflect the value of control principle veritably. Giving the appropriate sample size for each group rightly was the basic guarantee for the research result could be reproduced. Following the principles of randomized, controlled and repetition strictly could achieve an excellent balance between con-trol groups ultimately, that was to say that the balanced principle was a principle of gatekeeper.Conclusion: Following the four principles strictly is critically important to assure the result accurately and reliably in physiological research.

Key words: physiology, experimental design, random principle, control principle, repeat principle, balanced principle