Postoperative remifentanil-induced pain sensitization is common, but its molecular mechanism remains unclear. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been shown to have a critical role in morphine-induced hyperalgesia. This study was designed to determine how CaMKII phosphorylation and protein expression levels change in the central nervous system of rats with remifentanil-induced hyperalgesia.Male Sprague-Dawley® rats were exposed to large-dose (bolus of 6.0 µg/kg and 2.5 µg/kg/min for 2 hours) intravenous remifentanil to induce post-transfusion hyperalgesia. Levels of phosphorylated CaMKII (P-CaMKII) and total protein of CaMKII (T-CaMKII) were determined at different post-transfusion times by Western blot and immunostaining and were compared with controls.P-CaMKII increased significantly (P<0.05) at 0, 0.5, and 2 hours. However, P-CaMKII at 5 to 24 hours and T-CaMKII at 0 to 24 hours post-transfusion did not change significantly in rats' spinal dorsal horn, hippocampus, or primary somatosensory (S1) cortex (n=6 per group). Similarly, immunostaining showed stronger P-CaMKII immunoreactants (P<0.05) and more P-CaMKII- positive cells (P<0.05) in the spinal dorsal horn, CA1 region of the hippocampus, and S1 cortex of rats 0.5 hours post-transfusion compared with the control group treated with 0.9% sodium chloride (n=3 per group).These results suggest that a temporary rise in the P-CaMKII level in the central nervous system may correlate with remifentanil-induced pain sensitization in the postoperative period.