Erythropoietin (EPO) is an antiapoptotic, neuroprotective and antiinflammatory hormone. EPO antiseizure effect elicits but the molecular mechanism is still not fully understood. Status epilepticus(SE) trigger inflammatory mediators in brain, produces neuronal damage preferential in the hippocampus, the underlying mechanism is still unsettled. Nitricoxide (NO) is synthesized from L-arginine (L-Arg) by three different isoforms of NO synthase (NOS), i.e. the constitutive neuronal and endothelial NOS (nNOS and eNOS) and the inducible NOS (iNOS). NO has been involved in the pathophysiology of epilepsy, but available data are conflicting and the role of NO in epilepsy still remains to be clarified. However, SE increases microglia activity and induces iNOS expression in hippocampal neurons, leading to apoptotic neuronal cell death in the hippocampus. In this study, the possible modulatory effect of recombinant human erythtopoietin (rhEPO) pretreatment on NO synthases (NOS; neuronal, inducible and endothelial) expressionin hippocampus after pentylenetetrazole (PTZ) induced seizures were analyzed. PTZ is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Adult male Sprague-Dawley rats were used (seven animal/each group). PTZ (80mg/kg i.p) was given to induce generalized seizures. rhEPO (3000 IU/kg i.p) applied 24 h before PTZ administration. The control group was given saline, the EPO control group was given the same dose of EPO. After injection of PTZ, seizures were observed for two h and scored as seizure stage, latency. Under general anesthesia (pental sodium, 50 mg/kg) immediately brain removed and hippocampus was removed to examined NOS isoforms using immunohistochemistry. Data are expressed as mean± SD. Behavioral data were analyzed by one-way ANOVA followed by Duncan post host doc test. PTZ induced generalized seizures iNOS immunreactivity increased, eNOS immunreactivity decreased in hippocampus. EPO pretreatment significantly (p<0.001) reduced seizures stage (2.7 ±0.01 vs 4.8±0.2 PTZgroup), and did not effect seizure latancy. Besides, it increased markedly eNOS activity, decreased markedly iNOS activity, did not effect nNOS activity. The data suggest that anticonvulsant effect of EPO might be related to the decrease of iNOS and increase of eNOS.