It is known that Reactive Oxygen Species (ROS) induces the pathogenesis of various neurodegenerative disorders including P.D. . As discussed earlier, rotenone is a renowned neurotoxin to produce ROS by inhibiting mitochondrial electron transfer at complex I. In this connection, the current study was aimed at understanding whether Celastrol could attenuate rotenone-induced intracellular production of ROS in SH-SY5Y cells by using DCF-DA fluorescent dye (Fig. and). As expected, SH-SY5Y cell's exposure to rotenone (50 nM for 24 h) exhibited a significant increase in intracellular ROS levels leading to cytotoxicity. Interestingly, cells pre-treated with Celastrol (40 µM) significantly reduced rotenone-induced ROS production. This concept is in line with the report of , where 10 nM rotenone have shown ROS production after 30 min of exposure time in neuron glial cultures. In contrary with the present results reported that 10 µM of rotenone induces ROS production when treated for 24 hours. This may be due to; rotenone-induced ROS generation in vitro depends up on the type of cell line used, the concentration of rotenone used, and the time of exposure to rotenone . The present data supports the earlier experiments reported by and concluded that Celastrol can easily penetrate biological membranes and is able to protect undifferentiated neuronal cells against rotenone-induced injury.