Abstract Objectives To induce Neurolathyrism in guinea pig fed with Lathyrus sativus diet. Methods Twenty four guinea pigs were randomly distributed into 3 groups, 8 animals each. Groups I control fed with control diet, Group II low toxin group fed with 90% Lathyrus diet containing 100 mg β-ODAP/100 g Lathyrus and Group III fed with 90% Lathyrus diet with 1060 mg β-ODAP/100 gLathyrus. The experiment was for 2 months. Diet intake, body weight, protein carbonyl, catalase, MDA, specific activity of electron transport complexes I, II, III and IV in cortex and cerebellum were analyzed. Histopathological and morphological changes were studied by electron microscopy Results The diet intake and bodyweight was significantly reduced in both the experimental groups (II & III) as compared group I. Protein carbonyls levels were significantly increased in motor cortex region of group II & III as compared to group I. The catalase activity in cortex region was significantly decreased in group II & III compared to group I. The MDA levels in motar cortex region were significantly higher in the group II & III as compared to group I. Whereas the MDA levels in the cerebellum was significantly higher in group III as compared to group I. The activity of complex I and II of cortex was decreased significantly in group II and III as compared to group I. However, there was no significant change in specific activity of electron transport complex II and complex III. The nitrate levels in the group II & III were significantly higher than group I in the cortex region. However, there were no significant differences in the nitrate levels in the cerebellum region. Electron microscopic study of motor cortex showed that the extensive degeneration of motor neuron was observed in group II and III compared to group I. Conclusions Consumption of ninety % Lathyrus sativus dietfor 2 months induces neurolathyrism in guinea pigs. Funding Sources Indian Council of Medical Research, National Institute of Nutrition, Hyderabad, India.