Tetrodotoxin (TTX) is a potent marine neurotoxin named after the order of fish from which it is most commonly associated, the Tetraodontiforms, or the tetraodon pufferfish. In the present study the crude TTX was extracted from pufferfish Lagocephalus sceleratus collected from the Red Sea in Egypt. The LD100 and LD50 of crude TTX were found to be 8.33 and 6.26 mg/kg for the gonad extract and 41.8 and 27.9 mg/kg for the skin extract, respectively. This indicates that the gonad TTX is more lethal than the skin. The effects of both gonad and skin TTX extracts on the levels of brain serotonine, acetylcholine, histamine, norepinephrine, and epinephrine were studied in rats. Brain serotonine level was significantly increased and reached its peak level after 4 hours (P<0.001) of TTX administration. Brain acetylcholine, histamine, and norepinephrine levels were also significantly increased but reached peak level after 6 hours (P<0.001). The effect of the gonad extract was more significantly profound and of longer duration than the skin extract. On the other hand, brain epinephrine did not show any significant change during the experimental period.