Exposure to ionizing radiation represents a genuine increasing threat to mankind and our environment. Aphanizomenon flos-aquae (AFA) is a blue-green microalgal species that has antioxidant properties. The Aim of the work: this study aimed to elucidate the possible radioprotective effect of Aphanizomenon flos-aquae (AFA) on the liver of irradiated adult male rats using biochemical parameters, histopathology, and quantitative histochemistry. Material and methods: the current experiment was carried out on 48 adult male albino rats (Rattus rattus). Rats were randomly and equally categorized into four groups: 1) Group C: control rats left without treatment; 2) Group R: rats were exposed to 4Gy of gamma-radiation as a single dose; 3) Group AFA: rats were treated orally with 94.5mg/kg body weight/ day AFA for 3 weeks and 4) Group AFA+R: rats were administrated AFA for one week before and three weeks after irradiation. The experimental rats were sacrificed after 5 and 21 days post-irradiation. Results: exposed to gamma radiation showed many biochemical changes which included a significant increase in serum ALAT, ASAT, ALP activities, and MDA in the liver tissues. Many histopathological and histochemical changes were observed in the liver tissue, such as the corrugated and ruptured endothelial lining of the central vein which contained hemolysed blood cells, numerous vacuolated hepatocytes with increased signs of karyolysis and pyknosis in nuclei of hepatocytes, highly dilated and congested hepatic portal vein, numerous hemorrhagic areas, and distorted bile ducts. Highly increased collagen fibers were also observed after gamma irradiation in the liver tissue. Also, the irradiated group induced a significant increase in amyloid β-protein, while a significant decrease in PAS+ve materials, total protein, and total DNA content were detected. Supplementation with AFA showed a trend toward lowering the incidence of hepatic histopathological and histochemical changes induced by γ-radiation.                                      
Conclusion: according to the results obtained in the current study using Aphanizomenon flos- aquae as a natural agent showed a strong radioprotective role.