The effect of lead exposure on non-adrenergic non-cholinergic (NANC) relaxations in rat gastric fundus was evaluated in this work. Wistar rats were divided into four groups: The control group received tap water and the three other received 0.008% of lead acetate in their drinking water for 15, 30 and 120 days. NANC relaxations induced by electrical field stimulation (0.5–8Hz, 1ms, 60V) of gastric fundus strips was inhibited in all groups treated with lead. The strips from groups, control and 120 days of lead treatment (LEAD 120), were incubated with l-NOARG (100μM). The presence of this blocker did not produce any additional inhibition. Sodium nitroprusside (10 −10 –10 −6 M) and 8-Br-GMPc (3×10 −8 –3×10 −4 M) produced dose-dependent relaxations in strips of both groups control and LEAD 120, however, in the LEAD 120, the potencies were significantly reduced from 7.32±0.05 to 6.40±0.09 (n=5) and 4.26±0.06 to 3.69±0.05 (n=5), respectively. Our data suggest that the chronic exposure to lead inhibits NANC relaxations probably by modulating NO release from NANC nerves and/or by interacting with intracellular transducer mechanisms in rat gastric fundus.