Sildenafil is an active cGMP-specific phosphodiesterase type 5 inhibitor that is effective in the treatment of male erectile dysfunction. None of the previous studies havemeasured sildenafil or its possibly related neurochemical changes, but mainly they related their finding to sildenafil associated behavior changes. In this work, behavioral and brain neurochemical changes (excitatory and inhibitory neurotransmitters) associated with acute administration of sildenafil using male albino rats were investigated. Rats were divided into three groups (n=6); group1 received saline (1ml/kg), group2 received single doses of sildenafil (1.5mg/kg), while group 3 received single doses of sildenafil (100mg/kg). Administration was via the intraperitoneal route. Behavior scores using EPM and brain homogenate for neurotransmitters evaluation by HPLC were carried out 60min after administration. Sildenafil did not produce any changes in behavior using the EPM test; also it did not alter the brain levels of excitatory, inhibitory and dopamine. Sildenafil produced dose dependent decreases in plasma dopamine level by mechanism(s) needs more neurochemical investigation. The chronic effect of sildenafil should be taken into consideration.