Cadmium (Cd), considered as a toxic heavy metal, could affect the tissues by induction of a state of inflammation and oxidative stress. N-acetylcys- teine (NAC) is a synthetic material with free-rad- ical scavenging capability and potent antioxidant properties. NAC has been approved to be a signif- icant protective agent that helps prevent several chronic illnesses. This study was aimed to eval- uate the possible role of NAC against Cd-induced pancreatic damage using histological, immunohistochemical and biochemical investigations. Forty male rats (3 months) were divided into four groups (n=10): control group; N-acetylcys- teine group, rats received NAC orally (150 mg/ kg /day) for 30 days; Cd group, rats received Cd orally (4mg/kg/day) for 30 days; NAC + Cd group. On the 30th day, blood samples and pancreatic specimens were prepared for biochemical, his- tological, and immunohistological studies. Mor- phometrical and statistical measurements were done. The NAC + Cd group revealed significant- ly reduced proinflammatory cytokines (IL-1 beta and IL-6) and oxidative stress parameters (MDA and NO), significantly elevated anti-inflamma- tory cytokine (IL-10) and anti-oxidative stress parameters (SOD, CAT, GSH), and markedly de- creased TNF-alpha expression when compared to Cd group. NAC supplementation also improved Cd-induced pancreatic vacuolation, nuclear alterations, inflammatory cell infiltration, con- gestion, and significantly increased TNF-alpha expression. In conclusion, NAC is effective as a protective agent against Cd-induced pancreatic injury, due to its anti-inflammatory and antioxi- dant properties.