Recently use of endosulfan has aroused a great concern among clinical and basic neuroscientists as besides adult population even the children residing in some areas of touristic state of Kerala, India which are under constant spraying of endosulfan had shown symptoms of CNS dysfunctioning including cerebral palsy, retardation of mental and physical growth, epilepsy and various congenital anomalies. In spite of several studies demonstrating neurotoxic potential of endosulfan, very little is known about the mechanism of its neurotoxicity. In the present study an attempt has been made to delineate the mechanism by which endosulfan a chlorinated hydrocarbon insecticide exerts its neurotoxic potential at cellular level using PC12, a dopaminergic cell line. Cells exposed to endosulfan (0-100 µM) for 1, 24 and 48 h showed significant loss in cell viability /mitochondrial functioning in a dose- and time- dependent manner following MTT assay and LDH leakage assessment. An oxidative stress mediated neurotoxicity was evident where endosulfan (1uM, a non cytotoxic concentration) exposure is accompanied by increase in lipid peroxidation and lowering in antioxidant defense as malonaldehyde (MDA), a product of lipid peroxidation was enhanced by 49 and 62 % following 24 and 48 hours endosulfan exposure. A decrease in levels of GSH (41 & 68 %) along with catalase (39 and 52%) and SOD (26 & 44 %) activities was also evident 24 & 48 h post exposure. Induced expression of early response gene protein (c-Fos, P<0.001; c-Jun P<0.05 and GAP-43, P<0.05) during 1-24 h endosulfan (1 ?M) exposure was accompanied by PKC activation. The present results suggest possible role of PKC/early response gene mediated oxidative injury and mitochondrial dysfunction in endosulfan neurotoxicity.