Acetaminophen (AAP) is a commonly analgesic found in numerous non-prescription pharmaceuticals. High dose and chronic ingestion of AAP caused renal toxicity. This study is designed to assess the possible nephroprotective role of flaxseed oil (FSO) in male rats. Nephrotoxicity was induced in rats via ingested a single dose of AAP (3 g/kg). Five groups of rats were used; Control, AAP, FSO (1.5 ml/kg) + AAP, FSO (3 ml/kg) + AAP, and FSO (4.5 ml/kg) + AAP. Rats were received orally FSO for 30 days and at the 30th day received AAP 1 h before FSO. Serum renal function indices were determined. Also, antioxidants, oxidative stress, and pro-inflammatory cytokines indices were measured in serum. Ingestion of FSO (3 and 4.5 ml/kg) prior to AAP intoxication significantly decreased AAP-induced nephrotoxicity as evidenced by significant decrease in renal functions relative to the AAP group. Prevented the oxidative stress as evidenced by significant increases in SOD and GSH levels, concurrent with a significant decline in MDA level. Besides, there were significant decreases in IL-1α and TNF-α relative to the AAP group. FSO (3 and 4.5 ml/kg) preserved the renal parenchyma, glomerulus and tubules histological features induced by AAP. FSO (4.5 ml/kg) was markedly the most effective dose relative to the two other doses. In conclusion, FSO protects AAP-induced renal toxicity in a dose dependent manner via its potent antioxidant and anti-inflammatory activities.