In this research, curcumin microcrystal was produced using the wet milling method, and its pharmacokinetic behavior was compared after intramuscular (i.m.) and oral administration. The effects of milling time on the prepared curcumin microcrystal were investigated. Curcumin microcrystal was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), FTIR, and in vitro dissolution. The results showed that there were no obvious changes in the crystal structure between bulk curcumin and curcumin microcrystal. Significantly higher dissolution rate from curcumin microcrystal (83.5%) at 90min was observed, compared with that of bulk curcumin (74.1%). Furthermore, the in vivo pharmacokinetic behavior and muscular irritation after i.m. administration were also evaluated. The results showed that the release of curcumin lasted for 1 week by processing into microcrystal. The histological examination implied that curcumin microcrystal was safe for i.m. injection and was appropriate for the i.m. delivery of curcumin.