Background: Chromium (Cr) is a main environmental contaminant, famous for its major poisonous effects. Cr (VI) induces variable health hazards. Selenium (Se) is a micronutrient with anti-oxidant activity. Aim of Study: This study aims to demonstrate the protecting role of selenium in chromium-induced hepatotoxicity in adult male albino rat. Material and Method: Thirty six adult healthy male albino rats 3-6 months of age were divided into four groups (9 animals for each): Group I (control): Fed on balanced diet and water; group II (Se-group): Received daily dose of sodium selenite (0.25mg/kg B.W, dissolved in distilled water); group III (Cr-treated): Received daily dose of potassium dichromate (700ppm equivalent to 67mg/kg B.W, in distilled water); group IV; received potassium dichromate in combination with sodium selenite (as mentioned in groups II & III respectively). Blood samples were drawn from tail vein for biochemical examinations, and after sacrifice fresh liver specimens were collected for histological, immunohistochemical studies and real-time RT-PCR analysis of oxidative stress genes. Results: Chromium motivated oxidative stress process, through producing significant down regulation of the gene expression levels of the anti-oxidant genes (CAT, SOD1 and GPx) as compared to control rats, thus inducing different hepatic histopathological changes in the form of loss of the normal arrangement of hepatocytes with dilated central vein. Dilated congested portal vein with thick wall and mononuclear cellular infiltrations were noticed. In addition, fatty degeneration, vacuolization and degeneration of hepatocytes were observed. Moreover, bile ducts showed proliferation and stratifications of their epithelial lining and some sinusoids showed slight dilatation. These histopathological changes were associated with high statistical significant increase in serum level of (ALT, AST and total bilirubin) in group III (Cr -treated) as compared with groups (I and II). Se co - administration with Cr in group IV showed less histopathological disturbances and induced a statistical significant decrease in serum level of (ALT, AST and total bilirubin) as compared with group III (Cr-treated). Such changes may be attributed to up regulation of gene expression levels of anti-oxidants