Abstract: Background and Objective: Cajanus cajan is traditionally used for the treatment of various ailments due to its antioxidant properties. The present study investigated the effect C. cajan crude aqueous leaf extract (CCLE ) in rats with acetaminophen (APAP)-induced acute renal injury. Materials and Methods: Preliminary acute toxicity testing of the extract was conducted to determine the oral median lethal dose (LD50). Twenty rats were divided into five experimental groups labelled (A-E) of 4 rats per cage. Group A served as the normal control group and was given only water and feed. Rats in groups C, D and E received 100 mg kg–1 b.wt., of ascorbic acid, 200 and 500 mg kg–1 of CCLE, respectively once daily for 7 days via oral route using an oral cannula. Thirty min after the daily treatments, 600 mg kg–1 b.wt., of acetaminophen (APAP) was administered orally to rats in groups B-E. At the end of the treatments, blood samples were collected from the animals via retro-orbital puncture for the estimation of serum urea, creatinine and uric acid levels. The rats were sacrificed under anaesthesia and the kidneys were excised for histopathological analysis. Results: Acute toxicity testing showed that CCLE has an oral LD50 of 8000 mg kg–1 b.wt. Serum biochemistry showed a statistically significant increase (p>0.05) in creatinine and uric acid levels in all treatment groups when compared to normal control. Histopathological findings revealed the observable renal injury, with CCLE-treated groups showing more severe histomorphological alterations when compared to the APAP (negative) control. Conclusion: Data obtained suggest that acute toxicity was not observed with C. cajan administration up to 8 g kg–1, however, its co-administration with a high dose of acetaminophen does not protect the kidneys but rather aggravates the acute renal injury.