The link between autophagy, inflammatory bowel disease, ischemic injury and cancer had been established. Reasonable evidence is available for Cadmium (Cd) to be related to certain cancers. Sildenafil had been investigated to modulate oxidative stress mechanisms.is to investigate Cadmium-induced adrenal cortical autophagy and to declare possible modulation by sildenafil.Twenty four Wistar rats weighing 150 -200gm were randomly and equally assigned into: Control group, Sildenafil (20mg/kg/day orally) exposed group, Cadmium group (Cd chloride 1mg/kg/day Sc), Cadmium + Sildenafil group (rats received Cd concomitant with Sildenafil). Euthanasia was done 4 weeks from the beginning of experiment; adrenal glands were subjected to biochemical, histological, ultrastructural and immunnohistochemical assessment.Control and Sildenafil exposed groups exhibited nearly similar results. Cd had produced adrenal cortical apoptosis and ultrastructural derangement of cell organelles. Cd-induced autophagy was detected by ultrastructural abundance of enlarged lysosomes and significant (p<0.05) increase in the optical density of LAMP2 (Lysosomal associated membrane protein2) immunoexpression. Sildenafil taken with Cd had decreased adrenal cortical autophagy, significantly modulated the adrenal gland Superoxide dismutase (SOD) and Malondialdehyde (MDA) compared to Cd group. Also, the optical density of NF-κb and Caspase3 immunoexpression was significantly decreased in Cd+Sildenafil compared to Cd group.Cadmium might induce adrenal cortical autophagy in rats and Sildenafil might show an ameliorating effect probably through enhancement of antioxidant defense mechanism and modulation of NF-κb.