The present study was aimed to investigate the effect of 13-cis-retinoic acid (13-CRA) on hemolymph glucose levels in the fresh water edible crab, Oziothelphusa senex senex. Injection of 13-CRA significantly increased hemolymph glucose levels in a dose-dependent manner in intact crabs. Bilateral eyestalk ablation (ESX) resulted in significant decrease in hemolymph glucose levels. Injection of 13-CRA in to ESX crabs did not cause any significant changes in hemolymph glucose level as compared to ESX crabs suggesting that the effect of 13-CRA could be on the neuroendocrine system in the eyestalks increasing secretion of hyperglycemic hormone. To test this hypothesis, eyestalks were collected from control and 13-CRA injected crabs, and tested for hyperglycemic effect and also for the hyperglycemic hormone levels. The levels of hyperglycemic hormone and the hyperglycemic effect were significantly low in the eyestalks collected from 13-CRA injected crabs when compared with eyestalks from control crabs. From results, it is hypothesized that 13-CRA-induced hyperglycemia in the crab, O. senex, is mediated by triggering the release of hyperglycemic hormone from the eyestalk.