Background: Metabolic Syndrome (MS) is a complex multi-system disease. Traditional Chinese medicine (TCM) is satisfactory in preventing and treating MS. Syndrome differentiation is the basis of TCM treatment, which is composed of location and/or nature syndrome elements. Many studies have found TCM syndromes are correlated with biological indicators. However, there are various data that mainly come from point-to-point studies, which can’t fully summarize the many to many relationship of TCM syndromes and biological indicators. Thus, it is also hard to deal with the problem that several types of syndromes may possibly happen to a patient at once in the real world. The purpose of this study is to find out the potential relationship between microcosmic index and syndrome elements from a holistic view by means of multi-label learning (MLL) technique, and to provide a multi-label model for TCM syndrome differentiation. Methods: The standardization scale on TCM four diagnostic information for MS is designed, which is used to obtain the results of TCM diagnosis. The model of microcosmic syndrome differentiation is constructed based on 39 physicochemical indexes, such as BMI, abdominal circumference, blood pressure,platelet,fasting blood sugar, insulin, blood lipid,by MLL techniques, called ML-kNN. First, the multi-label learning method is compared with three commonly used single learning algorithms. Then, the comparison of results of ML-kNN between physicochemical indexes and TCM information is also made. Next. the influence of parameter k of ML-kNN to the diagnostic model is investigated and then the best k-value is chosen for the TCM diagnosis. Results: A total of 698 cases are collected for the modeling of the microcosmic diagnosis of MS. The comprehensive performance of the ML-kNN model works obviously better than the others, whose average precision of diagnosis reach 71.4%. The results of ML-kNN based on microcosmic indexes are close to the results based on TCM information. The k value has less influence on the prediction results of ML- kNN. Conclusions: The MLL techniques facilitate building microcosmic syndrome differentiation model in MS and the experiments show this is a practical approach to solve the problem of labeling multiple syndromes simultaneously. Besides, it is also suggested that there is many to many relationships between TCM syndrome elements and physicochemical indexes, which will be conducive to the future objective and comprehensive study of syndrome differentiation in MS.