A plant alkaloid obtained from Curcuma longa, curcumin possesses anti-oxidant and anti-inflammatory effects. Nanoformulations have been developed for preclinical studies which demonstrate enhanced therapeutic efficacy. Effect of acute intraperitoneal (i.p.) administration of curcumin C3 complex nanoparticles [1,5, 10, 20, 40, 80mg/kg, (i.p.)] 75min prior to PTZ, on clonic seizure thresholds induced by intravenous infusion of pentylenetetrazole (PTZ) 0.5% was investigated in comparison with curcumin (40 and 80mg/kg, i.p.) in male mice. Moreover, to clarify the probable role of NO in the anticonvulsant property of nanocurcumin, non-effective doses of l-arginine (l-Arg), a NO donor; 7-nitroindazole, 7-NI, a preferential neuronal NO synthase inhibitor; L-NAME, a non-selective NO synthase inhibitor and aminoguanidine (AG), a selective inducible NO synthase inhibitor (iNOS), in combination with nanocurcumin (80mg/kg, i.p.), 15-30min before it were employed. While curcumin did not show any anticonvulsant effect, nanocurcumin revealed dose-dependent anticonvulsant property at the doses 20, 40 and 80mg/kg, P<0.01, P<0.01 and P<0.001, respectively. l-Arg (30 and 60mg/kg) dose-dependently reversed the anticonvulsant effect of the most effective nanocurcumin dose (80mg/kg), P<0.01 and P<0.001, respectively. On the other hand, L-NAME (3 and 10mg/kg, i.p.) markedly potentiated the sub effective dose of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. Similarly, AG (50 and 100mg/kg, i.p.) profoundly augmented the seizure thresholds of nanocurcumin (10mg/kg), P<0.01 and P<0.001, respectively. In addition, 7-NI (10, 30 and 60mg/kg, i.p.) failed to influence the responses. These data may support excess of NO production following PTZ infusion probably resulting from iNOS source. Consequently, nanocurcumin probably down regulated NO. To conclude, nanocurcumin showed anticonvulsant effect. Furthermore, this effect was reversed following l-arginine as an external NO precursor. However, both the non-selective NOS inhibitor and selective iNOS inhibitor increased the thresholds. It is evident that nanocurcumin may influence the seizure thresholds at least in part through a decrease in NO.