The dissipation of ciprofloxacin (CIP, 1.0 and 10.0mg/kg) and kresoxim-methyl (KM, 1.0 and 2.0mg/kg) in manure-amended soil, the variations in soil enzyme activities and microbial functional diversities, and CIP-induced bacterial community tolerances were studied using a chromatographic analysis, enzyme colorimetric and titration analyses, and the BIOLOG EcoPlate method. Three successive treatments of individual and combined samples of CIP and KM at low and high concentrations were performed at 60d intervals. The dissipation half-life of CIP increased, but that of KM decreased in manured soil with treatment frequency; furthermore, the combined treatment altered the dissipation rates of CIP and KM. A stronger inhibitory effect on the activities of soil neutral phosphatase and urease was observed in the individual KM treatment than in the individual CIP treatment. A similar inhibitory trend was also found in soil neutral phosphatase activity in the combined treatment at high concentration compared to that at low concentration, but the activity of soil catalase was enhanced in the early stages of the KM or CIP treatments. Meanwhile, the inhibitory trend on the overall activity and functional diversity of soil microorganisms was observed in the individual KM or CIP treatment, and the combined treatment exerted a greater suppression effect than that in the individual treatment. Bacterial community resistance to CIP increased significantly with increasing treatment frequency and concentration, and furthermore antibiotic resistance developed faster in the combined treatment than in the individual treatment. It was concluded that the repeated treatments of CIP and KM could alter their dissipation rates and soil enzyme activities, suppress microbial functional diversity, and increase bacterial community resistance to CIP in manured soil.