This study examined the analgesic effect of diprospan in rats with trigeminal neuralgia. Rat model of trigeminal neuralgic pain was established by loosely ligating the left infraorbital branch of the trigeminal nerve. After allodynia developed, the rats were randomly divided into 2 groups (n=20 in each): diprospan group, in which the rats received diprospan (7 mg/mL, 0.1 mL) injected to the left infraorbital foramen area; control group, in which saline (0.1 mL) was administered as the same manner as the diprospan group. The pain threshold (PT) in the left infraorbital area was measured before and 2, 6, and 8 weeks after the administration. The expression of neuropeptides [substance P, preprotachykinin A (PPTA), calcitonin gene-related peptide (CGRP)] in the trigeminal nerve was detected at the same time points as the PT measurement by immunohistochemistry or in situ hybridization method. The results showed that in the diprospan group, the PT was 10.65 ± 1.26, 10.77 ± 1.19 and 14.13 ± 1.34 g 2, 6, and 8 weeks after the administration respectively, significantly higher than that before the administration (PT value: 0.36 ± 0.11) (P<0.05 for each). In the saline group, the PT was 0.37 ± 0.13, 0.66 ± 0.09, 4.45 ± 1.29 and 13.72 ± 1.72 g before and 2, 6, and 8 weeks after the administration respectively with differences being significant between before and 6, 8 weeks after the administration (P<0.01). No significant difference existed in the PT between the diprospan group and the saline group at pre-administration (P>0.05). The PT in the diprospan group was significantly greater than that in the saline group 2 and 6 weeks post-administration (P<0.05). In the diprospan group, the expression levels of neuropeptides were significantly reduced as compared with those in the saline group 2 and 6 weeks post-administration (P<0.05). It was concluded that diprospan has an obvious analgesic effect on the trigeminal neuropathic pain partly by reducing the expression of neuropeptides in the trigeminal ganglia.