This study was designed to assess the effects of experimental diabetes and nerve crush injury upon vasoactive intestinal polypeptide (VIP) content and axonal transport in the dorsal root ganglia (DRG) and sciatic nerve. Sciatic nerve crush injury in control and 3-week streptozotocin-diabetic rats was followed 6.5 days later by placement of 2 constricting ligatures above the site of injury. After 12 h, the L4 and L5 DRG and sciatic nerve were removed for VIP radioimmunoassay. Similar samples were also taken from control and diabetic rats whose nerve had been ligated without a preceding crush. VIP was increased over 2-fold in ganglia and 4-fold in nerves of crush-injured controls compared to uninjured controls (both P < 0.01). Crush injury also increased ganglion and nerve VIP in diabetic rats (P < 0.05 and 0.01, respectively) but the increase was less than what occurred in crush-injured controls (both P < 0.05). The accumulation of VIP proximal to a sciatic ligature was similar in control and diabetic rats and was not altered in either group by crush injury, while retrograde transport of VIP was initiated by crush injury in both control and diabetic rats. These data show that short-term diabetes does not alter the amount and peripheral axonal transport of VIP in the sciatic nerve but impairs the ability of peripheral nerve to respond to injury.