The present study investigates the possible mechanism of erythropoietin (EPO) mediated benefits in mouse model of streptozotocin (icv) induced dementia. Morris water maze test was employed to assess memory of the mice. Biochemical-estimations like brain acetyl cholinesterase (AChE) activity, brain nitrite/nitrate and total oxidative stress levels were also performed. Streptozotocin (STZ) produced a significant decrease in water maze performance of mice reflecting impairment of memory. STZ also produced a rise in brain AChE activity, nitrate/nitrite & oxidative stress levels. Treatment of EPO (i.p.) attenuated STZ-induced memory deficits & biochemical changes. Further, the noted beneficial effect of EPO on STZ- dementia was significantly abolished by pre-treatment of L- NAME a non selective inhibitor of nitric oxide synthase (NOS), 7 NI a selective nNOS inhibitor, and L NIO a selective eNOS inhibitor. However, no such effect was seen with pre-treatment of aminoguanidine a selective iNOS inhibitor. It may be concluded that the beneficial effects of EPO in STZ dementia involve nitric oxide dependent pathway with eNOS and nNOS playing a crucial role while sparing the iNOS pathway.