Objective: To observe the effects of p38 mitogen activated protein kinase (MAPK) inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods: Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency (PWL), histology and the spinal levels of IL-1β and TNF-α were detected. Results: All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed.However, following intrathecal injection of SB203580, the left PWLs (12.12±1.26 s at 16 days and 12.99±1.65 s at 19 days)were significant higher than that of controls (9.05±1.08 s at 16 days and 8.55±1.60 s at 19 days), P＜0.05. Meanwhile,intrathecal injection of SB203580 evidently reduced the levels of spinal IL-1βand TNF-α. Conclusion: Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting intracellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.