Tri-ortho-cresyl phosphate (TOCP) is an organophosphorus ester. It is capable of producing organophosphorus ester induced delayed neurotoxicity (OPIDN) in human being and sensitive animals, which is characterized by ataxia that progresses to paralysis after 1-3 weeks following exposure to some organophosphorus ester. In present study, 18 adult hens were divided randomly into three groups, i.e. two experimental groups and control group (n = 6 each group). All hens were 10 months old and weighted 1.5-2.0 kg. The hens in two experimental groups were treated with TOCP by gavage at single dosages of 375 and 750 mg/kg respectively. TOCP was dissolved in corn oil and administered at 0.65 ml/kg. Six control hens received an equivalent volume of corn oil by gavage. All hens were sacrificed after 21 days of treatment and the sciatic nerves were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilament (NF) subunits were decreased both in supernatant and pellet of sciatic nerves, and the most noticeable decrease in levels of NF subunits protein was observed in neurofilament medium (NF-M). Compared to the control hens, neurofilament heavy (NF-H) level decreased by 36 and 38% (P < 0.01) in the pellet and by 27 and 26% (P < 0.05) in the supernatant of sciatic nerves of hens treated with 375 and 750 mg/kg TOCP respectively. The reduction of NF-M were 36 and 68% (P < 0.01) in pellet, 50 and 67% (P < 0.01) in supernatant at 375 and 750 mg/kg dosage respectively. The neurofilament light (NF-L) lessened slightly, but the relative percentage of integrated optical density (IOD) was no significant alteration when compared to the control hens. There were significant decreases in levels of alpha-tubulin, beta-tubulin in pellet and alpha-tubulin, beta-tubulin, beta-actin in supernatant of sciatic nerves in TOCP-treated hens. Thus, the decreases of cytoskeletal proteins suggested the possible involvement of them in delayed neurotoxicity.