Wide-spread application of animal manure as fertilizer to agricultural lands has caused great concern over the release of organic contaminants such as veterinary antibiotics into the environment. Tylosin, a macrolide class of veterinary antibiotic compounds, is widely used in intensive animal production for preventing and treating diseases as well as promoting growth.  This study investigates the sorption-desorption, transport, and degradation properties of tylosin in soil, water, and manures as impacted by different environmental factors.  In doing so, a series of experiments based on batch, column and microcosm incubation approaches were carried out to elucidate controlling mechanisms of tylosin behavior in various matrices. Tylosin sorption in soil and manure was found to be greatly affected by matrix pH, organic matter, ionic strength and redox potential. Increasing pH and ionic strength generally decreased tylosin adsorption by clay minerals, and sorption of tylosin by montmorillonite was much higher than that by clay mica and kaolinite. X-ray diffraction analysis suggested that tylosin was intercalated into Montmorillonite upon adsorption. Overall, the results suggest that tylosin in soil, water and manure are significantly influenced by various physical and chemical conditions and careful assessment of these conditions is necessary in order to manage its behavior in the environment.