Introduction: With extensive applications of nanoparticles including titanium dioxide nanoparticles (TiO2 NPs) in different fields, many adverse effects may threat both environmental and medical health. Aim of this work: To evaluate the role of n-acetyl cysteine (NAC) against TiO2 NPs intestinal toxicity in adult albino rats. Material and methods: Fifty adult male albino rats were classified into five groups. Group I: negative control received regular diet and water. Group II: positive control administered 1ml of 5% gum acacia solution once a day. Group III: gavaged orally with NAC (100 mg/kg). Group IV: orally gavaged with TiO2 NPs (1200 mg/kg) once a day. Group V: orally gavaged once daily with TiO2 NPs (1200 mg/kg) and NAC (100 mg/kg). After 6 weeks, all rats were weighed and blood sample were submitted to estimate serum level of citrulline. Then parts of ileum from all rats was dissected and subjected to interleukin 6 (IL6), interleukin 10 (IL10) and tumor necrosis factor (TNF-α) estimation, histopathological examination and determine the extent of DNA damage by gel electrophoresis. Results: The results revealed that TiO2 NPs induced significant decreases in body weight, and serum level of citrulline with significant increases in IL6, TNF-α and significant decrease IL10 in tissues of ileum. These were associated with histopathological changes in the ileum and DNA damage detected by gel electrophoresis. Co-administration of NAC with TiO2 NPs provided protection against these changes. Conclusion: TiO2 NPs exposure causes inflammation in ileum with DNA damage and administration of NAC offers protection against its damaging effects.