Zenarestat (FK-366; FR-74366) is an aldose reductase (AR) inhibitor investigated as a treatment for diabetic neuropathy and cataract. Zenarestat is a highly specific AR inhibitor, it did not affect the activities of enzymes in the glycolysis pathway, the pentose-phosphate pathway and NADPH-dependent enzymes such as NOS and glutathione reductase. Zenarestat exhibited some inhibition of aldehyde reductase, the most closely related enzyme to AR, however, its IC50 was evidently higher than that for AR. Zenarestat dose-dependently reduced the elevated sorbitol concentration in the lens, retina sciatic nerve, and renal cortex. The most potent effect of zenarestat was seen in the sciatic nerve. Zenarestat inhibits cataract formation and to counteract reduced motor nerve conduction velocity in the streptozotocin-induced diabetic rat. Zenarestat had been in clinical trials for the treatment of diabetic neuropathy however future development was discontinued due to dose-dependent renal toxicity.