Objective To understand the distribution and diversity of tetracycline resistance genes in human, animal and environmental micro-ecology in different countries. Methods Metagenomic sequencing data of 2 036 micro-ecological specimens from different sources were identified tetracycline resistance genes, distribution and mechanism of tetracycline resistance genes from different sources, different countries and different sites of human body were studied. Results Among 2 036 specimens, detection rate of tetracycline resistance genes was 44.70% (n=910), with the highest detection rate in human specimens (78.99%, 880/1 114), followed by animal specimens (40.98%, 25/61). A total of 28 kinds of tetracycline resistance genes were detected, 248 specimens were detected at least 10 kinds of tetracycline resistance genes, human specimens were detected all 28 kinds of tetracycline resistance genes, animal specimens were detected 6 kinds of tetracycline resistance genes. Among 28 tetracycline resistance genes, 10 coding ribosomal protective protein genes were found, 5 of which (tetQ, tet32, tetW, tetO, tetM) were detected in more than 50% of human specimens, and 4 were detected in animal specimens with a detection rate of more than 16%. 338 human specimens had national information (China, Denmark, Spain, the United States and Japan), analysis on drug resistance genes showed that tetO, tetQ and tetW were detected in 5 countries; specimens from China were matched 24 tetracycline-resistant genotypes, among which tet32, tet40, tetO, tetQ and tetW were detected in all Chinese specimens. Among the distribution of tetracycline resistance genes in micro-ecology of different sites of human body, intestinal tract had the richest distribution of drug resistance genotypes, 26 kinds of tetracycline resistance genes were matched to intestinal specimens, detection rates of tetQ, tetW, tetO, tet32 and tet40 were more than 70%. Conclusion There are a large number of tetracycline resistance genes in human and animal micro-ecology, which threaten the public health and ecological environment, and need to be paid more attention.