Context: The main objective of the current study is to improve the water solubility of florfenicol (FF) and evaluate changes in its pharmacokinetics and anti-inflammatory activity. Materials and methods: Florfenicol nanocrystals (FF-NC) were prepared by wet grinding combined with spray drying. The characterisations, pharmacokinetics, and anti-inflammatory activity of FF-NC were evaluated. Results: The particle size, polydispersity index (PDI), and zeta potential of FF-NC were 276.4 +/- 19.4 nm, 0.166 +/- 0.011, and -18.66 +/- 5.25 mV, respectively. Compared with FF, FF-NC showed a better dissolution rate in media at different pH. Pharmacokinetic experiments showed the area under the curve (AUC(0-)(t)), maximum concentration (C-max), and mean residence time (MRT) of FF-NC were about 4.62-fold, 2.86-fold, and 1.68-fold higher compared with FF, respectively. In vitro anti-inflammatory experiments showed that FF inhibited the secretion of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and synthesis of NO in a dose-dependent manner, while FF-NC showed a stronger anti-inflammatory effect than FF under the same dose. Conclusion: FF-NC are an effective way to improve the bioaffinity and anti-inflammatory effects of FF.