It has been a hot issue in the field of tradition Chinese medicine(TCM) to find a technical solution to the safety of traditional Chinese medicine injections(TCMIs). Based on oral drug absorption law, the present article will put forward that the macromolecular impurity that cannot directly absorbed is one of the important factors leading to its safety problems, which mechanisms may be associated with pathogen associated molecular patterns(PAMP) and damage associated molecular patterns(DAMP) that can directly stimulate the body’s natural immune response, then cause anaphylactoid reactions. Finally, the article suggests that macromolecular impurity removal is a feasible strategy to improve the safety of TCMIs.