Puffer fish poisoning remains a severe seafood poisoning condition blamable for numerous human intoxications. Research on puffer fish poisoning enables studying the involvement of puffer fish poisoning in human security. The current study thus intention of investigating whether Arothron hispidus from the south-east coast of India (Palazhyar) cause for the neurodegeneration. Cresyl violet stained sections of the rat brain regions examined for pathological changes in rats treated with A.hispidus toxic extract. We noticed disarrangement and neuron loss in the primary motor area, hippocampus, amygdala, thalamus, temporal lobe, parietal lobe, and cerebellum regions of rats treated with A.hispidus skin extract. Damaged regions directly or secondarily associated with sensory and motor functions, this may cause loss of sensory and motor function. From our observation, we conclude that neuronal loss of a rat's brain treated with skin extract as clear through histopathological analysis, due to the neurotoxic effect of Arothron hispidus.