We investigated the possible induction of apoptosis of dorsal root ganglion (DRG) neurons and the defect of nerve regeneration after crush injury with reference to the JNK/c-jun and cAMP pathway in streptozocin-induced diabetic rats. In addition, the effects of a PGE1analogue were tested in diabetic rats. At day 0 (before axonal injury), no TUNEL-positive DRG neurons were observed in any group. From day 1 to 7 after axonal injury, TUNEL-positive DRG neurons were seen in diabetic rats, but not in non-diabetic or PGE1-treated diabetic rats. The regeneration distance at day 7 after crush injury was shorter in diabetic rats than in the other groups of rats. The time course of JNK/c-jun phosphorylation did not parallel apoptosis. At day 7, the cAMP content of DRG was higher than that at day 0 in non-diabetic and PGE1-treated rats, whereas it was not increased after 7 days in diabetic rats. These results indicate that in diabetic rats apoptosis of DRG neurons is induced by axonal injury independently of the JNK/c-jun and cAMP pathway and that PGE1rescues DRG neurons from apoptosis and improves axonal regeneration in diabetic rats.