The objective of this study was to prepare micronized cefquinome sulfate by negative-pressure cavitation antisolvent precipitation to improve its permeability and transdermal absorbability. Dimethylsulfoxide and ethanol were used as the solvent and anti-solvent, respectively. The effects of operating parameters, including cefquinome sulfate concentration, volume ratio of antisolvent to solvent, antisolvent precipitation time, and applied negative pressure on the characteristics of the precipitate crystals, were evaluated using an orthogonal array design. Under the optimized conditions, micronized cefquinome sulfate with a mean particle size of 415.8 nm was obtained at a yield of 78%. The micronized cefquinome sulfate was characterized by scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. No obvious change in its chemical structure was observed, but crystallinity was reduced. The physicochemical properties and transdermal absorbability of crystalline cefquinome sulfate improved as a result of the particle size reduction by physical modification. This negative-pressure cavitation antisolvent precipitation process offers a promising technique for improving the physicochemical properties and anti-inflammatory activity of cefquinome sulfate. (C) 2016 Elsevier B.V. All rights reserved.