Abstract: In the Republican period, health service was gradually incorporated into the national legal system, and the Nanjing national government formulated the Rules for the prepared drugs administration to establish a dual management system of centralized laboratory testing and parallel registration by local authorities, and to rectify and regulate the prepared drug market. The formulation of this rule was affected by the political disputes among factions and the controversy over the abolition of Chinese medicine. Besides, the introduction of the rule caused many contradictions due to technical errors in the legislation itself and the enforcement of the law that touched on the interests of many parties, which made the implementation of the rule ineffective. In order to solve the problem of the prepared drug administration, the health department of the national government and the pharmaceutical companies have repeatedly communicated with each other, re-organized the general registration of the prepared drug, simplified its registration procedures, and substantially amended the Rules for the prepared drugs administration, partially satisfying the demands of pharmaceutical companies and reducing the interests of local authorities. The evolution of the rules shows the twists and turns in the formulation and implementation of special regulations in the game of interests in a specific historical period.