Untreated streptozotocin-induced diabetes results in highly significant and reproducible alterations to peripheral nerve function. Thus, motor and sensor nerve conduction velocities (NCV) were decreased by approximately 21% and 14%, respectively whilst parameters of resistance to hypoxic conduction failure (RHCF) were increased by approximately 50%. NCV deficits were established after one month of untreated diabetes whilst increased RHCF continued to develop over at least two months of untreated diabetes. Dietary treatment of diabetic rats with evening primrose oil (EPO), thus overcoming the inhibition of -6 desaturase was able to prevent decreases in motor and sensor NCV whilst partially preventing the development of increased RHCF. Sciatic endoneurial capillary density was also increased. The effects of EPO were seen to be dependent on cyclo-oxygenase mediated metabolism and this, combined with the lack of effects with sunflower oil suggested gamma-linolenic acid (GLA) to be the active component in EPO. Thus, reversal and preventive treatment of diabetic rats with purified GLA, as well as iloprost (a prostacyclin (PGI2) analogue), had very similar effects to EPO. Therefore, it is likely that increased vasodilator PGI2 production underlies the mechanism of action. However, these highly beneficial effects of GLA (-6 essential fatty acid (EFA)) treatment were in contrast to the poor effects of the -3 EFAs found in fish oil. Furthermore, these -3 EFAs attenuated the actions of GLA. Both observations are linked to a possible attenuation of PGI2 synthesis and increased vasoconstrictor thromboxane (Tx) production. Several different GLA containing oils were found to be significantly less effective than EPO in the reversal of diabetic nerve conduction abnormalities.