Freshwater lakes provided an ideal media for the accumulation and propagation of antibiotic resistance genes (ARGs), because they were susceptible to anthropogenic impacts. Land reclamation and urbanization exerted severe anthropogenic impacts on lakes from middle and lower reaches of the Yangtze River, China over the past decades. In this study, 15 lakes in the region were selected to understand the level and variability of ARGs. Proportion of different land use types was applied to display the land reclamation and urbanization around each lake. For sulfonamide resistance (sul) genes, sul1 had the highest relative abundance in sediments, with maximum 2.11 101 copies/16SrRNA copy in Gehu Lake. For tetracycline resistance (tet) genes, tetG had the highest average value of relative abundance (4.74 103 copies/16SrRNA copy), followed by tetB, tetA, tetQ and tetM. Class I integron (intI1) played an
important role in acquisition and dissemination of sul1 and tetG. Sediment characteristics (moisture, density, total nitrogen, total carbon, ammonium, and nitrate) were found to have no significant effect on ARG distribution. Taihu Lake and Yangcheng Lake which exhibited high sul and tet genes had the high proportion of built-up land use.