Zinc is an important trace element in biological systems; however, excessive extracellular zinc could lead to neuronal cell death following ischemia, seizures, and brain trauma. In this study, we investigated whether the intracortical injection of zinc sulphate (200 mu g/kg, i.c.) changes total number of Purkinje cells in the cerebellum and whether different types nitric oxide synthase inhibitors. N-(G)-nitro-L-arginine methyl ester (L-NAME), N(omega)-nitro-L-arginine (L-NNA), aminoguanidine and 7-nitroindazole (7-NI), have protective effects against zinc neurotoxicity in Wistar albino rat;. Animals were divided into 6 groups: control, zinc, zinc + L-NAME (100 mg/kg, i.p.), zinc + L-NNA (100 mg/kg, i.p.), zinc + 7-NI (100 mg/kg, i.p.) and zinc + aminoguanidine (100 mg/kg, i.p.) groups. Total number of Purkinje cells in the cerebellum was estimated using unbiased stereological technique as 318,947 +/- 20,549, 123,483 +/- 23,762, 206,537 +/- 43,128, 178,135 +/- 26,635, 193,148 +/- 46,104 and 212,910 +/- 26,399 in the control, zinc, zinc + L-NAME, zinc + L-NNA, zinc + 7-NI and zinc + aminoguanidine groups, respectively (mean +/- SD). The number of Purkinje cells in zinc group was significantly lower than that of the other groups (P < 0.001). It was found that the nitric oxide synthase inhibitors have neuroprotective effect against zinc neurotoxicity on Purkinje cells. These data show that the inhibition of the nitric oxide synthase could prevent some of the deleterious effects of zinc on Purkinje cells. (C) 2010 Elsevier B.V. All rights reserved.