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Abstract Urolithiasis is still a major disease of the urinary tract. Urolithiasis formed when substances in the urine such as calcium, oxalate, and phosphorus become highly concentrated. Intraperitoneal injection of sodium oxalate (NaOx) to rats is a good standard animal model of urolithiasis. Thus, the purpose of this study aimed to evaluate the ameliorative role of the Ananas comosus ethanolic extract (ACEE) when administered orally to male urolithiatic rats induced by NaOx. Forty two male Wistar albino rats were divided into three groups. All groups treated for 7 consecutive days, the control group administered distilled water orally. ACEE group received ACEE (1000 mg/ kg b.wt) orally. Urolithiatic group which administered NaOx (70 mg/ kg b.wt, i.p.) and subdivided into subgroups. Urolithiatic subgroup co-treated with distilled water orally. Urolithiatic subgroup co-treated with ACEE (500, 750 and 1000 mg/kg b.wt) orally. Urolithiatic subgroup co-treated with standard anti-urolithiatic drug (cystone) (750 mg/kg b.wt) orally. At the end of 7 days, urine sample was collected during 24hour. Urine volume and pH were measured and the urine supernatant was used for analysis of calcium, phosphorus, magnesium, creatinine, urea, and uric acid. The collected serum was used for kidney function markers besides calcium, phosphorus, and magnesium. Further, Kidney oxidative markers were determined. The present study revealed that urolithiasis increased kidney function markers, calcium and phosphorus significantly and decreased in magnesium level. Urolithiasis induced OxS in rats, which have bad impacts on kidney functions confirmed by the histopathological examination. Conversely, ACEE or cystone improved most of the biochemical parameters and reduced OxS induced by urolithiasis. Also, histopathological examination showed an improvement in the kidney architectures of the treated groups as compared to urolithiatic group. In concolusion, ACEE has noteworthy anti- urolithiatic efficacy for inhibition of renal calculi probably by affecting calcium oxalate crystallization |